Term
| Typical ion concentrations |
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Definition
Steady-state concentrations, proper homeostasis, NOT equilibrium states
Greater intracellular concentration - K (10x), Mg (2x)
Greater extracellular concentration - Na (10x), Ca (1000x), Cl (5x) |
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Term
| Lipid bilayer components and effect of cholesterol |
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Definition
Phoshpolipids, cholesterol, sphingolipids, glycolipids
Cholesterol decreases permeability, less mobile/deformable components; different lipid components on inside and outside faces due to different function |
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Term
| 3 types of protein-mediated membrane transport |
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Definition
| Simple diffusion, facilitated diffusion, active transport |
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Term
|
Definition
| Random movement of molecule fueled by thermal energy of normal kinetic motion of matter until equilibrium reached; can be helped by channel protein or facilitated carrier protein or occur through bilayer on its own |
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Term
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Definition
| Need carrier protein, usually occurs against concentration gradient until steady state is reached |
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Term
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Definition
| Uses energy from ATP hydrolysis directly |
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Term
| Secondary active transport |
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Definition
| Use potential energy stored in ionic gradients provided by primary transporters (not directly from ATP); movement of 1 solute coupled to movement of 2nd solute whose gradient set up by primary transport |
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Term
|
Definition
| Randomly cross membrane, high to low concentration, no NET movement at equilibrium, requires no energy; essential for gas transport (oxygen uptake in lungs) |
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Term
|
Definition
Flux (J) = D(ΔC)/(Δx)
J = rate of net diffusion per unit are per unit time
D = diffusion coefficient
(ΔC)/(Δx) = concentration gradient across membrane; C = concentration difference, x = thickness |
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Term
|
Definition
| Unstired layer near membrane leads to apparent increase in diffusion barrier thickness |
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Term
|
Definition
K - ratio of solute's solubility in oil to solubility in water; lipid bilayer is hydrophobic so being more oil-like increases flux
K = 0 for charged substance, K>1 = hydrophobic, K<1 = hydrophilic |
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Term
|
Definition
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Term
|
Definition
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Term
|
Definition
| Permeability coefficient of solutes with same diffusion coefficient depends on partition coefficient (applies to small molecules <5 C since similar permeability) |
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Term
| Pharmaceuticals that target TM proteins that help molecules cross lipid bilayer |
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Definition
Diuretics - Na/K/Cl cotransporter - loop of Henle, treat HTN
L-DOPA - AA transporters in CNS, convert to dopamine - Parkinson's
PPI - ATP-dependent proton pump - treat acid reflux
Anti-depressant - Na-driven transporters |
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Term
|
Definition
| Specific carrier protein carry solute through membrane via series of conformational changes; rate of diffusion approaches maximum rate (saturation curve like Michaelis-Menten); used by glucose, many amino acids |
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Term
| Carrier-mediated transporter properties (3) |
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Definition
| Stereospecificity, saturation, competition |
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Term
| Facilitated diffusion rate-limiting step |
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Definition
| Conformational change that occurs for each molecule, limits rate to 10^2 to 10^4/second; also limited by finite # transport molecules at saturation |
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Term
| Rocking banana/Alternating access model |
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Definition
| Conformational change occurs for each molecules; can open both ways, however it always occurs high to low concentration |
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Term
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Definition
| IM proteins that transport glucose, some transport additional molecules; enter cells at metabolically appropriate rate |
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Term
|
Definition
GLUT1 - RBC, vascular epithelium (BBB), D-glucose, mannose, galactose; deficiency --> seizures w/ low glucose in CSF
GLUT4 - insulin-regulated, adipose and skeletal muscle
GLUT5 - fructose transport in small intestine, deficiency --> dietary fructose intolerance |
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Term
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Definition
| Facilitated transport, nerve excitation, muscle contraction; specific to 1 type of ion; much faster because no conformational change (10^8/sec), rate-limiting step: opening the pore |
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Term
| Primary active transporters (3) |
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Definition
| P-type transporters, F-type and V-type transporters, ABC transporters |
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Term
| P-type transporter examples |
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Definition
| Na pump, Ca pump, proton pump |
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Term
|
Definition
| Maintain ionic homeostasis in all cells, 1/3 metabolic rate; electrogenic (1+ to outside); 3 Na in, 2 K out, uses 1 ATP; both move against gradient; inhibited by cardiac glycosides (digoxin) in treatment for CHF |
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Term
| Na/K ATPase osmotic balance |
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Definition
| Fixed anions in cytosol, osmotic gradient pulls water in; Na going out of the cell keeps some Cl out to decrease osmotic gradient |
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Term
| Na/K ATPase conformational changes |
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Definition
| E1 (open to inside), E2 (open to outside), cyclic change with PHOSPHORYLATED INTERMEDIATE (P), uses 1 ATP - representative for primary proton pumps; each state selectively binds one ion type |
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Term
|
Definition
| Very low intracellular Ca, pump into ECM and into ER/SR; 1-2 Ca ions per ATP hydrolysis |
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Term
|
Definition
| Parietal cells of stomach gastric glands and kidney; inhibited by PPIs like omeprazole to treat GERD |
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Term
|
Definition
| No E-P intermediate formed; mitochondria and chloroplasts; runs backwards to synthesize ATP, H+ moves down concentration gradient |
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Term
|
Definition
| No E-P intermediate formed - intracellular organelles (lysosomes), pump H into organelle to acidify |
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Term
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Definition
| Highly conserved ATP-binding cassette; includes CFTR, MDR transporter (multidrug resistance pump) which pumps toxic substances out of cell; intracellular domain where ATP is hydrolyzed, hydrolysis drives movement |
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Term
|
Definition
| Cystic fibrosis transmembrane regulator - secretes Cl in some epithelial cells; mutation quickly leads to cystic fibrosis; speed of transporter, really a channel though |
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Term
|
Definition
| Problem with ABCA1/CERP mediating efflux of cholesterol and phoshpolipids |
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Term
|
Definition
| Two substances move in 1 direction with obligatory coupling; 1 molecule (usually Na) down concentration gradient |
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Term
|
Definition
SGLT1 - main mechanism of glucose absorption in GI, 1 or 2 Na+ per glucose
Na/K/2 Cl cotransporter in ascending limb of loop of Henle - form urine, inhibit by furosemide |
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Term
|
Definition
| Two substances move in opposite directions with obligatory coupling; 1 solute pumped out against electrochemical gradient |
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Term
|
Definition
Na/Ca exchanger in myocyte to keep Ca low in cell: 3 Na/1-2 Ca
Na/H - pH regulation - maintain cell volume, electroneutral
Cl/HCO3 exchanger
Mitochondrial ADP/ATP exchanger - move ATP into IM space and ADP into matrix after oxidative phosphorylation |
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Term
|
Definition
| Movement from high water concentration to low water concentration; movement of water from low solute concentration to high solute concentration; no energy needed |
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Term
| Water movement driving force |
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Definition
| IMPERMEANT SOLUTES DRIVE WATER MOVEMENT; driving force is osmotic pressure (Δπ) |
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Term
| 2 solutions with semi-permeable membrane |
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Definition
| Water moves from high to high water/low solute to low water/high solute until same concentration on both sides |
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Term
|
Definition
Concentration of osmotically-active particles; O = gC (g = particles per mole in solution, C = concentration)
Colligative property (NaCl: 2, CaCl2: 3) |
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Term
| Isoosmotic, Hyperosmotic, Hypoosmotic |
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Definition
Isoosmotic - 2 solutions have same osmolarity
Hyperosmotic - solution with higher Osm
Hypoosmotic - solution with lower Osm |
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|
Term
| Standard intracellular osmolarity |
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Definition
| 300 mOsm unless otherwise stated |
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Term
|
Definition
Ease of solute crossing membrane; 0-1, dimensionless
0 = freely permeable, 1 = permeable, urea = 0.02
Substances with high reflection coefficient drive osmosis |
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Term
|
Definition
| Δπ = σRT*Δ(gC) - Osmotic pressure related to reflection coefficient, osmolarity difference |
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Term
|
Definition
| Water movement across cell membrane, biological property of solution; dependent upon concentration of impermeant solutes; observed property |
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Term
| Cell reaction to hypertonic/hypotonic solution |
|
Definition
Hypertonic - cell shrinkage
Hypotonic - cell swells |
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Term
|
Definition
| Tonicity = σgC; depends on permeability |
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Term
|
Definition
| Tonicity and osmolarity are the same |
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|
Term
| 150 mM NaCl, 100 mM urea outside |
|
Definition
| hyperosmotic solution, isotonic solution |
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|
Term
| Infusion of 1.5 L isotonic saline into ECF |
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Definition
| Same OsM inside and outside, ECF volume increase, cells unchanged |
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Term
| Infusion of 1.5 L solute-free water into ECF |
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Definition
| Lower OsM outside cell; water flows into cell, increased volume in ECF and in cells with decreased Osm |
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Term
| Ingestion of 225 mmoles NaCl into ECF |
|
Definition
| Higher OsM outside cell; water flows out of cell, increased volume in ECF, decreased volume in cell; increased OsM in both |
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Term
|
Definition
| Specialized membrane water transporter molecules (family) with different tissue distributions, mechanisms of regulation, ability to transport small neutral molecules; present in cells with increased H2O permeability |
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Term
|
Definition
| Allows water transport only, tetramer with hourglass-shaped pore |
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Term
|
Definition
| Allows water and glycerol transport |
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Term
|
Definition
| Proximal tubule (1,7), descending thin limb (1), collecting ducts (2-4); water moves freely in these areas, make isoosmotic urine |
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|
Term
| Water permeability in kidney |
|
Definition
Regulated by ADH
ADH present: AQP2 XP increase, H2O out, concentrated urine
ADH absent: AQP2 XP decrease, H2O more in, dilute urine
Diuretic increases production of urine |
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Term
|
Definition
| Vm, voltage difference between inside and outside of cell; outside of cell defined to be V=0 |
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|
Term
|
Definition
Almost always negative
Neuron = -60mV, Skeletal muscle = -90mV, Smooth muscle = -50mV, RBC = -8mV; substantial variability in different cell types in these categories too |
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|
Term
| Cell permeable to K and Cl: 100 mM KCl cell, 100 mM KCl solution |
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Definition
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|
Term
| Cell permeable to K and Cl: 100 mM KCl cell, 10 mM KCl solution |
|
Definition
| K and Cl diffuse out of cell |
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|
Term
| Cell permeable to K only: 100 mM KCl cell, 10 mM KCl solution |
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Definition
| K leaves cell down concentration gradient, Cl stays in cell, charge imbalance leads to membrane potential; membrane potential just enough to counterbalance force of diffusion (stop K from leaving); most cells very permeant to K |
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|
Term
| Membrane potential requires: |
|
Definition
| Concentration gradient, selectively permeable membrane |
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Term
|
Definition
Ex = -(RT)/(zF)*ln([Xi]/[Xo]) = (-60mV/z)*log([Xi]/[Xo]), z = valence of ion X; calculated for any permeant ion
Also known as equilibrium potential or diffusion potential |
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|
Term
|
Definition
| Vm = Ex, e.g. K+ = -60 mV |
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|
Term
|
Definition
Vm-Ex; when non-zero, ion has net low across membrane
E.g. Vm = -90 mV, Ek = -60 mV; ions flow into cell
Positive = outward movement, Negative = inward movement |
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|
Term
| Na and K enter and exit cell |
|
Definition
| Na leak channels, K leak channels, Na:K pump |
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|
Term
| If Na and K have same permeability, only ions involved |
|
Definition
| No Vm set up because ions pump and leak in and out evenly |
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|
Term
| K permeability greater than Na, only ions involved |
|
Definition
| More K leaks out of cell than Na leaks in; Vm set up to counteract excess K leak, need to decrease K exit and increase Na intake; negative Vm outside, Vm should be closer to Ek than Ena |
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Term
|
Definition
| Vm = Ek (and opposite if Pna>>>Pk) |
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|
Term
| Goldman-Hodgkin-Katz equation |
|
Definition
K, Na, Cl are permeant ions
Vm = complicated equation with Permeabilities and concentrations multiplied and added
Numerator: internal K, internal Na, external Cl
Denominator: external K, external Na, internal Cl
Increasing membrane permeability to ion moves Vm toward Ex of that ion |
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|
Term
|
Definition
| Vm = -60mV*log(([K]I + α[Na]i)/([K]o + α[Na]o), where α=PNa/PK, α=0.01 in resting muscle cell or neuron |
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|
Term
|
Definition
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|
Term
|
Definition
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|
Term
| Ion exchange through Na/K ATPase |
|
Definition
| 3 Na out, 2 K in, electrogenic, makes inside more negative; increases membrane potential of cell ~5 mV |
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|
Term
| Active vs. passive ion distribution |
|
Definition
Na, K actively distributed, sets up Vm
Cl passively distributed, set up by Vm so Ecl = Vm; no specific pump for Cl to set up a gradient |
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Term
|
Definition
| Rapid and transient alteration in Vm, uniform in size and duration; all-or-none |
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|
Term
| Phases of action potential |
|
Definition
| Resting level, rising phase, oversheet, peak, repolarization, afterhyperpolarization |
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Term
|
Definition
| Undershoot; Vm comes back down and overshoots the resting potential, phase with the most negative Vm, making it more difficult to fire another action potential |
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|
Term
| Alpha value during action potential |
|
Definition
| Initially very low (0.01), Na channels open faster, becomes very high (20), K channels open and decreases (1) and Na channels close and returns to resting (0.01) |
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Term
|
Definition
Rest: Activation gate closed and inactivation gate open
Depolarization opens activation gate, Na flow
Inactivation gate closes stopping Na flow (absolute refractory)
Inactivation gate re-opens, activation gate closes, return to rest |
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|
Term
|
Definition
Increases slower during depolarization, does not inactivate
1 activation gate open as long as membrane is depolarized, not at rest or when hyperpolarized |
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|
Term
| Example of inhibition action potential |
|
Definition
| Scorpion venom - slow close of Na channels, inhibit inactivation so membrane potential stays high for long time, AP travels very slowly |
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|
Term
| Absolute refractory period |
|
Definition
| No action potential can be stimulated no matter what because Na channels are inactivated |
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|
Term
| Effective refractory period |
|
Definition
| Cannot elicit propagated action potential regardless of stimulus (important for cardiovascular physiology, coordinating atria and ventricle contraction) |
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|
Term
| Relative refractory period |
|
Definition
| Larger-than-normal stimulus for action potential during AHP due to extra low Vm |
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|
Term
| Channels used in action potential |
|
Definition
| Voltage-activated channels used in both Na and K permeability pathways |
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Term
|
Definition
| Depolarization of 1 part of axon leads to weaker depolarization of adjacent portion; impulse can die out if it becomes too weak |
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Term
|
Definition
| Insulate to ensure propagation, breaks at Nodes of Ranvier (0.2-2 mm), Na channels only at high density at nodes of Ranvier |
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Term
|
Definition
| How quickly signal de-amplifies; proportional to membrane resistance (Rm) and inversely proportional to axial resistance (Ra) |
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Term
|
Definition
| Membrane resistance; proportional to length constant - increased by addition of myelin sheath |
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Term
|
Definition
| Axial resistance; inversely proportional to length constance - resistance of flow along length; higher diameter leads to smaller Ra (squid giant axon) |
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Term
|
Definition
| Small (~3 nm), gap junctions as electrical connection; hemichannels connect cells, leads to electrical syncytium; depolarization of 1 cells leads to simultaneous contraction of many cells; UNITARY |
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Term
|
Definition
| Half provided by each cell, only work if both present; in electrical synapse |
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Term
|
Definition
| ~30-50 nm, release NT as chemical signal; MULTI-UNIT; ions flow through postsynaptic channel |
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Term
|
Definition
Increase extracellular Ca --> EPSP amplitude increase (more enter cells)
Increase extracellular Mg --> EPSP amplitude decrease (interfere)
Raise both, EPSP, very little depolarization, not past threshold; occasional MEPP |
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Term
|
Definition
| Miniature excitatory Postsynaptic Potential - smallest release of 1 quanta of ACh (one synaptic vesicle) |
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|
Term
| Series of events at neuromuscular junction |
|
Definition
| Excite motor neuron --> release ACh --> travel through synaptic cleft to AChR --> depolarize (endplate potential) --> action potential in muscle fiber |
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Term
| Axon terminal Ca channels |
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Definition
| Voltage-gated; AP leads to influx of calcium, high intracellular Ca; synaptic vesicles with ACh bind to membrane and exocytose |
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Term
|
Definition
| Non-selective cation channels which cause alpha = 1, leading to depolarization (Vm=0), crossing of threshold and firing action potential; 1 motor neuron --> 1 myofiber at NMJ |
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Term
|
Definition
| Ligand-gated ion channel, nonselective cation pore, trigger for opening is ACh binding --> depolarization of endplate, triggering of action potential |
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|
Term
| Excitatory neurotransmitters |
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Definition
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|
Term
| Inhibitory neurotransmitters |
|
Definition
| GABA, glycine - lead to IPSP |
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Term
|
Definition
| Benzodiazepine binding site, leads to greater IPSP (pentobarbital) |
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Term
|
Definition
| Light meromyosin (tail) and heavy meromyosin (globular head); usually 2 heavy chains and 2 light chains; light meromyosin is essential and regulated especially in smooth muscle |
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Term
|
Definition
| Globular head region (S1) with ATP-binding site and actin-binding site; small flexible tail piece (S2) act as hinge to transduce motion |
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|
Term
|
Definition
Essential and regulated especially in smooth muscle
Essential light chain - myosin stability
Regulatory light chain - modulate muscle function |
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|
Term
| Myosin tails and filament formation |
|
Definition
| Assemble myosin molecules into thick filaments; tail-to-tail in center first, head-to-tail extension in both ways, helical arrangement along length |
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|
Term
|
Definition
| Many isoforms; vary in intrinsic ATPase activity which determines Vmax; govens rate of movement of crossbridges during contraction; much slower ATPase in smooth muscle |
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|
Term
|
Definition
| G-actin (globular, monomeric), F-actin (filamentous, polymeric) - two intertwined strands of polymers in thin filaments |
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Term
|
Definition
| Protein along groove of actin helix, spans 6-8 monomers |
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Term
|
Definition
TnC binds calcium
TnI binds actin, inhibits actin-myosin binding |
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Term
|
Definition
| Very large protein extending Z-line to M-line for horizontal stability, prevent sarcomere overextension; contributes to parallel elasticity, passive resistance to stretching |
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Term
|
Definition
| Wraps around thin filament, sets length of the filament |
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Term
|
Definition
| Capping protein, protect actin filament from depolarization |
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Term
|
Definition
| Capping protein, protect actin filament from depolarization |
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|
Term
|
Definition
| Anchors thin filament to Z-line via CapZ |
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|
Term
|
Definition
| No change in length in thin/thick filaments, only variable degree of overlap; Z-lines move closer together, I-band gets narrower as interdigitation and crossbridges increase in skeletal muscle |
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|
Term
| Crossbridge Cycle for Striated muscle |
|
Definition
| Myosin bound by ADP + Pi; Ca increase , bind TnC, tropomyosin uncover binding site, cross bridge form; release ADP + Pi, stretch S2 hinge, 45 degree angle for myosin head; S2 hinge recoil, power stroke movement, actin-myosin bound; ATP binds myosin, releasing crossbridge; ATP hydrolysis returns head to 90 degree angle, cycle continues until Ca low |
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|
Term
|
Definition
| S2 hinge recoiling pushing thin filament to sarcomere center; 10 nm per stroke per sarcomere; needs to be repeated many times; crossbridges asynchronous during contraction so it is smooth |
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|
Term
| Filament movement in isotonic contraction |
|
Definition
| Muscle length changes, force constant, multiple cycles lead to myosin binding actin site further along sliding filament |
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|
Term
| Filament movement in isometric contraction |
|
Definition
| Same length; force increasing; muscle held so it cannot shortn; crossbridge at/near same actin site repeatedly, minimal sliding |
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|
Term
| Force generated in relation to sarcomere length |
|
Definition
Longest sarcomere = no overlap, force = 0
Shorten sarcomere, more overlap, linear increase, reach Lo for optimal force, most crossbridges
Linear decrease <2µm, less interactions, steeper at 1.67, greatly reduced at 1.6 when Z-lines meet |
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Term
|
Definition
| Length of optimal force; 2µm in skeletal muscle; Lo at resting site because we need to generate maximum amount of force right from the start |
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|
Term
| Activation of striated muscle |
|
Definition
| Dis-inhibition of tropomyosin, actin-regulated |
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|
Term
|
Definition
| T-tubule + 2 terminal cisternae in skeletal muscle; site of coupling excitation of T-tubule and Ca release from SR |
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Term
|
Definition
| 1 terminal cisterna + T-tubule in cardiac muscle |
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|
Term
|
Definition
| Extension of sarcolemma, winds through and encircles each myofibril, connects electrical signal at outside of cell to sarcomere |
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Term
|
Definition
Voltage-sensor protein in T-tubule membrane, controls permeability of C2 release channels in SR via foot processes;
voltage-gated L-type Ca channel |
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Term
|
Definition
| Ryanodine receptor, Ca release channel in SR |
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|
Term
| Skeletal muscle contraction initiation |
|
Definition
| AP enters T-tubule, DHPR sense change in Vm, DHPR conformational change causes RyR in SR to open, release Ca into intracellular space; Ca binds TnC and initiates crossbridge cycling |
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|
Term
| Ca source in skeletal muscle |
|
Definition
| ALL comes from Sarcoplasmic Reticulum |
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|
Term
| ATP hydrolysis in skeletal muscle contraction |
|
Definition
| Contracts sarcomere, reduces intracellular Ca |
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|
Term
| Termination of skeletal muscle contraction |
|
Definition
| Ca ATPase in longitudinal SR takes up Ca actively; diffuses to terminal cisternae where Ca bound to calsequestrin to store until next excitatory event; RyR closes and returns to rest until next AP (helped by binding proteins); [Ca] decreases, disassociates from TnC leading to steric blocking and inhibition |
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|
Term
| Cardiac cell in relation to skeletal cell (size, SR) |
|
Definition
| Smaller, surface can affect interior easier, less extensive SR, smaller terminal cisternae |
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|
Term
| Ca source for cardiac muscle contraction |
|
Definition
| Most comes from SR, some needed from ECM (Trigger calcium) |
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Term
|
Definition
| Fully functional voltage-gated L-type Ca channel, calcium released by this is not enough to initiate contraction (need trigger calcium) |
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|
Term
| Cardiac muscle contraction initiation |
|
Definition
| Ca enters from ECM during AP by DHPR, Ca binds RyR which releases more Ca (CICR) |
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|
Term
|
Definition
| Calcium-induced calcium release - ONLY IN CARDIAC MUSCLE - Ca from DHPR binds RyR to release more Ca to have enough for initiating contraction; allows for MODULATION in size of contraction |
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|
Term
| Heart contraction/beat changes, maximum |
|
Definition
| Heart can change rate AND strength of beat, pump up to 25 L/minute with increased cardiac output` |
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|
Term
| Cardiac muscle relaxation |
|
Definition
| Ca ATPases in SR and surface membrane, Na/Ca exchanger in surface membrane (Na down gradient, Ca against gradient), most Ca pumped back into SR |
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|
Term
| Na/Ca exchanger in cardiac muscle |
|
Definition
| Na enters cell down gradient, Ca exits cell against gradient during relaxation; Na gradient originally setup by the N/K ATPase; process drives Ca export |
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|
Term
|
Definition
| Ability to modulate magnitude or rate of force production/contractility |
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|
Term
| Effect of changing Ca entry into cardiac muscle |
|
Definition
| Change amount of Ca released by CICR, change force generated; prolong or attenuate AP plateau phase can affect Ca influx (e.g. myocyte beta-1 adrenergic receptor increases all) |
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|
Term
|
Definition
| Agonist of active myocyte beta-1 adrenergic receptor; increase heart rate |
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|
Term
| Effect of increasing extracellular Ca on cardiac muscle |
|
Definition
| Increase EC Ca --> increase Ca entry --> increase CICR (opposite of decreased EC Ca) |
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|
Term
|
Definition
| Ca needed from ECM to initiate cardiac muscle contraction; no contraction in Ca-free solution |
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|
Term
| Cardiac muscle sensitivity |
|
Definition
| Can modulate sensitivity of contractile proteins; Ca-sensitizers increase response of myofilaments to Ca without change in cytoplasmic Ca; "work better" to generate more force; Levisomendon in Europe, will be drugs here soon |
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|
Term
| Protein Kinase A on cardiac muscle contraction |
|
Definition
| Phoshporylates cardiac TnI, decrease Ca TnC affinity, increase rate of relaxation; phosphorylates phospholamban on SR to increase Ca ATPase activity, enhance relaxation |
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|
Term
|
Definition
| Phosphorylated by PKA, located on SR, increases Ca ATPase activity, leads to faster relaxation |
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|
Term
| Temporal summation in skeletal muscle |
|
Definition
| Ca transients from 2+ close AP's sum to produce more force; repetitive stimulation of muscle at frequency to not allow complete relaxation; can occur because 1 AP does not release all stored Ca in SR; increased force due to more crossbridges |
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|
Term
|
Definition
| Fused contraction, smooth increase in force to max due to max activation of muscle from repetitive stimulation at high frequency; frequency limited by electrical properties, refractory period |
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|
Term
| Tetanus in different muscle types |
|
Definition
Skeletal + smooth - electrical event is brief, temporally separate from mechanical phase; tetanus possible because refractory period over before peak force is reached
Cardiac: electrical + mechanical events in similar time course, no tetanus possible |
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|
Term
| Spatial summation in skeletal muscle |
|
Definition
| Total sum of force made by each muscle fiber depends on total # of muscle units activated; increase # of motor neurons firing (recruitment) |
|
|
Term
|
Definition
| Increase number of motor neurons (motor units) firing to increase force; total # of fibers in unit determines force output |
|
|
Term
| Small vs. large motor units and where found |
|
Definition
Small motor unit - 306 fibers, extrinsic muscles of eye
Large motor unit - hundreds of fibers, leg muscles; larger diameter cell bodies and axons; faster conduction velocity |
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|
Term
|
Definition
| Recruitment of motor units within muscle starts with smallest cell bodies (small motor units) since it is easiest to pass firing threshold and progresses larger and larger; distribution so % force increase which each unit adds is constant - smooth gradation of force with additional recruitment |
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Term
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Definition
Generation of force, no change in length; no work done; force expressed in terms of cross-sectional area
Length = constant; force = bell curve |
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Term
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Definition
| Muscle shortening, constant force |
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Term
| Phases in isotonic contraction |
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Definition
1 - Isometric contraction, force increases, no isotonic
2 - Isotonic shortening, constant force, move load
3 - Isotonic relaxation, constance force, let go of load
4 - Isometric relaxation, length constant, decrease force |
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Term
| Length-force relationship for single muscle filament |
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Definition
| Bell-shaped curve, force depends on overlap of thick and thin filaments |
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Term
| Whole muscle total force factors |
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Definition
| Active contractile elements and passive contractile elements (CT, membranes, collagen, elastin) - determine contributions of total force derived from passive to total force measured-difference is active force |
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Term
| Elasticity of resting muscle |
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Definition
| Resting muscle imperfectly elastic; resists stretch by exerting passive/resting force; length of resting muscle and force it exerts is non-linear; stretching leads to extension of CT elements - initially compliant then sharply resist as stretched |
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Term
| Elastin and collagen in elasticity of resting muscle and force-length curve |
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Definition
Elastin is very compliant, contributes to "foot" of curve
Collagen is very non-compliant, contributes to sharp rising portion of curve |
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Term
| Increased collagen in striated muscle |
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Definition
| Seen in disease states and aging; muscle becomes stiffer and less compliant (e.g. aortic stiffening leading to increased arterial pressure) |
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Term
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Definition
| ΔLength/ΔForce = ΔL/ΔF; Collagen/Elastin ratio sets the compliance |
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Term
| Length-tension curve for resting muscle stretched |
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Definition
| Short muscle length - all total force is active; longer length has more passive forces; decreasing active force at some point due to less filament overlap |
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Term
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Definition
| Optimal length for making maximum isometric force; optimal overlap of thick and thin filaments |
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Term
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Definition
| Heart at max Lo when it is filled, starts below Lo; smooth muscle more like cardiac muscle; Lo is longer than the resting length |
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Term
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Definition
| Resting length of cardiac muscle |
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Term
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Definition
Systole = Contractile
Diastole = Filling of heart |
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Term
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Definition
| Force on a muscle prior to stimulation based on length; sets the potential crossbridges that can form and maximal force that CAN be developed; think of as a stretching that sets the maximal force |
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Term
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Definition
| Load or resistance which the muscle must contract against (weight being lifted, e.g.) |
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Term
| Preload and afterload in heart function |
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Definition
Preload - how much the heart has filled
Afterload - force to move blood out of heart |
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Term
| Force peak if weight can/cannot be lifted |
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Definition
Can lift weight - flat part in force-time chart as object lifted
Cannot lift - bell-shaped curve as no shortening occurred |
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Term
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Definition
Time to develop isometric force; measure as function of load
Small load - develop small force fast
Bigger load - longer delay to shortening, develop more isometric force |
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Term
| Effect of preload increase |
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Definition
| Length at which no movement increases (Fmax), maximal velocity (Vmax) unchanged |
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Term
| Maximal velocity of shortening |
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Definition
| Governed by intrinsic rate of crossbridge cycling with ATP hydrolysis as rate-limiting step depending on isoform of ATPase; invariant in skeletal muscle really; can modulate in cardiac muscle |
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Term
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Definition
| Continuously ongoing or maintenance of a steady tonic force for a long period of time, e.g. vasoconstriction to maintain arterial pressure or direct blood flow, peristalsis; large movement much slower than skeletal muscle |
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Term
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Definition
| Blood vessels, airways, bladder, intestines, uterus (childbirth) |
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Term
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Definition
| Among smallest cells in body, spindle-shaped, 50-200µm long, 2-8µm wide; disordered |
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Term
| Smooth muscle thick filaments |
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Definition
| Myosin (smooth isoform) with low ATPase activity, 100x slower than skeletal muscle, causing slow contraction; can generate great force since more time spent in contraction; 20% myosin of skeletal muscle uniformly dispersed parallel to long axi |
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Term
| Smooth muscle thin filaments |
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Definition
| Actin (many isoforms), tropomyosin in grooves to stabilize filament; 2x amount in skeletal muscle, various isoelectric points |
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Term
| Role of tropomyosin in smooth muscle |
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Definition
| Stabilize thin filament; DOES NOT inhibit actin-myosin interaction |
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Term
| Intermediate filaments in smooth muscle |
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Definition
| Attach to cytoplasmic dense bodies - desmin and/or vimentin |
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Term
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Definition
| Desmosome in smooth muscle - thin filament anchorage point for transmission of force; several actin filaments pass through/terminate in dense body |
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Term
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Definition
| Binds Ca, CaM, actin, Myosin Binding Protein in smooth muscle; inhibits actin-activated myosin ATPase activity; reversed by high [Ca], calmodulin or phosphorylation |
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Term
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Definition
| Associated with actin filaments in smooth muscle; binds Ca, CaM, actin-binding protein; inhibits actin-activated myosin ATPase activity |
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Term
| Troponin in smooth muscle |
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Definition
| NO TROPONIN IN SMOOTH MUSCLE |
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Term
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Definition
| Binds Ca, important for phosphorylation and activation of contraction in smooth muscle |
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Term
| Methods of direct Ca entry in smooth muscle |
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Definition
| Leak channels, Stretch-activated channels, Ligand-gated channels, Voltage-gated channels |
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Term
| Leak channels in smooth muscle |
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Definition
| Tonicly active, Ca move down concentration gradient and membrane potential; insufficient to trigger contraction on its own (unless pathological state) |
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Term
| Stretch-actived channels in smooth muscle |
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Definition
| Membrane tension causes opening, e.g. filling state in bladder or heart (myogenic response) - leads to Ca entering |
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Term
| Ligand-gated channels in smooth muscle |
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Definition
| Bind agonist (e.g. norepinephrine), also known as receptor-operated channels (ROC) |
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Term
| Voltage-gated channels in smooth muscle |
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Definition
| Sense membrane depolarization, blocked by DHPs, allow entry of enough Ca to trigger contraction without CICR, modulatable graded contraction |
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Term
| Second messengers in smooth muscle |
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Definition
| Indirectly entry, G-protein activates PIP2 pathway --> IP3 and DAG; IP3-gated Ca channels on SR open and release Ca into cell (pharmacomechanical coupling); RyR can perform CICR, just need enough Ca to induce this |
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Term
| Na channels vs. Ca channels in smooth muscle |
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Definition
| No Na channels, just Ca channels; Vm increase, Ca enters and can trigger contraction |
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Term
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Definition
| SR Ca ATPase, surface Ca ATPase, cell surface Na/Ca exchangers, variable |
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Term
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Definition
| Activation of myosin, in contrast to striated muscle's dis-inhibition of actin |
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Term
| Smooth muscle myosin-actin interaction |
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Definition
| Depends on phosphorylation of 1 myosin light chain (MLC); only crossbridges when phosphorylated; MLCK and MLCP phosphorylate/dephosphorylate myosin light chain |
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Term
| Smooth muscle contraction initiation |
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Definition
| [Ca] rise, Ca binds CaM, Ca-CaM activates MLCK, phosphorylate MLC, initiate crossbridge cycling; MLCK in balance with MLKP and can both be regulated by second messenger systems |
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Term
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Definition
| Rho Kinase - phosphorylates MLC, inhibits MLCP by phosphorylating myosin-binding unit - leads to overall increased force of contraction |
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Term
| Protein Kinase C on smooth muscle |
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Definition
| PKC phosphorylates CPI-17, binds and inhibits MLCP, increases contraction |
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Term
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Definition
cGMP --> PKG --> MLCP --> relaxation
NO --> guanylyl cyclase --> cGMP, blood vessel constriction |
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Term
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Definition
| cAMP --> PKA --> increase Ca pumping back into SR + MLCP activity increase --> relaxation; particularly in skeletal muscle blood vessels and airway smooth muscle after beta-2 adrenergic receptor activated; pathway activated by inhalers |
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Term
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Definition
Maintain high level of tone or force over long time with little energy utilization in smooth muscle
Ca enters; MLC phosphorylation, force development, MLC dephosphorylation to basal level, force remains; dephosphorylated latchbridges have low cycling rate, slow shortening velocity |
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Term
| Smooth muscle length-tension relationship |
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Definition
| Broader curve (force generated over wider area), significant amount of passive force at Lo due to network of CT supporting smooth muscle to prevent overextension |
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