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how organism functions; subcellular level to intact organism |
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all vital processes occur at this level |
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cells specially adapted to perform one/more functions; organized into tissue, organs, organ systems |
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functional division of tasks to specific areas |
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maintenance of constant internal environment despite changes in external environment; steady-state balance |
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how it's controlled; cellular level = DNA, local level = cell factors/paracrine reactions, systemic level = neural and endocrine |
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over what time period (short = ms/sec, intermediate = sec/min, long = hrs/days) |
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stimulus and response of system work in opposite directions; changes invoked by effectors that return system to homeostasis; occurs when sensors detect a change from desired self-point and actual level = error signal |
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stimulus and response of system work in same direction (reinforcement); doesn't increase indefinitely - terminated when initiating signal removed or when body is limited in ability to increase response; cellular level = depolarization - opening VG Na+ channels; systemic = reproduction |
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provides short communication b/w cells; most molecules present in living systems = highly soluble in H2O; temperature control |
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60% of total body weight; can vary w/age/gender; extracellular fluid (ECF) + intracellular fluid (ICF) = TBW |
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extracellular fluid (ECF) |
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all fluid outside of cells; 20% of body weight; divided by capillary wall into: interstitial fluid (ISF) + plasma volume (PV) = ECF |
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15% of body weight; fluid surrounding cells but not in blood vessels (vascular system) |
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5% of body weight; fluid portion of blood (w/in vascular system) |
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intracellular fluid (ICF) |
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40% of body weight; fluid w/in cells |
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body weight = kg TBW = L density water = 1 kg/L therefore 1 L water = mass of 1 kg |
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Na+ = major cation, major determinant of ECF osmolality; Ca2+ = impt. cation involved in altering cellular function; Cl- and HCO3- = major anions capillary wall freely permeable to small ions = composition ISF and PV similar (PV contains more proteins) |
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maintained by various specific membrane transport proteins; K+ = major cation; Na+ and Ca2+ = low; PO4- and proteins = major anions |
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units concentration of solutes |
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# molecules = millimole mM; # charged particles = millequivalent mEq; # of particles = milliosmole mOsm (osmolality = osmole/kg, osmolarity = osmole/L) |
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exchange b/w fluid compartments |
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water moves freely; all exchanges of water and solutes w/ external environment occur throuh ECF; changes in ICF secondary to fluid shifts b/w ECF and ICF; ECF and ICF in osmotic equilibrium except for brief periods; body sensors monitor osmolarity (hypothalamus) |
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kidney; evaporation; sweat; feces; increased temp and exercise |
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force generated by pumping of heart and effect of gravity on a column of blood in vessels |
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osmotic pressure of plasma proteins |
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determined by: osmotic pressure arising from solute differences b/w fluid compartments |
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highly compartmentalized; contain protein structures and organelles that perform specific functions |
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permeability barrier that separates ECF from ICF; establishes what substances can cross into/out of the cell; contains surface antigens (self v. non-self); cell communication through receptors/signal transduction pathways for hormones/neurotransmitters; variety of adhesion molecules; fluid mosaic model; composed of lipids and proteins |
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1. phospholipids = major component of plasma membrane; polar (hydrophilic) phosphate head grp, w non-polar (hydrophobic) tails = amphipathic; bilayer; hydrophobic tails = permeability barrier to water soluble molecules (most abundant is choline containing phospholipids) 2. cholesterol - hydrocarbon ring structure; stabilizes membrane @ normal body temp; increases membrane fluidity; reservoir of precursor molecules for steroid hormones |
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100+ different; integral/intrinsic = embedded in membrane; transmembrane protein (carriers and channels) - span membrane completely; peripheral/extrinsic = on outside or inside of surface, often enzymes (phosphatase = remove phosphate grp from protein, kinase = add phosphate grp to protein) |
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1. diffusion 2. use of intrinsic/integral proteins |
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permeability layer to water soluble molecules; free passage of lipid (non-polar) molecules = O2, CO2, alcohol, steroid hormones, fatty acids |
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integral/intrinsic proteins |
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means for passage of water-soluble, polar, charged molecules; certain size restrictions, different transport proteins depending on type of protein |
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transmembrane protein that has a central water-filled passage, or pore; aquaporins, ion channels |
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water channels - main route for water movement into and out of cell; continuously open; increase/decrease in # of channels affects water permeability |
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gated channels - modifications that allow channel to be opened or closed; classified by selectivity (diameter ion, shape of channel, electrical charge of channel), conductance (measure of how readily an ion moves through the channel), type of gating (leak, voltage gated, ligand/chemical, mechanically gated, intracellular messenger gated) |
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high open probability therefore allows relatively free movement of ions (K+) |
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voltage gated (VG)channels |
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respond to alterations in membrane potential (Na+, K+, Ca2+, Cl-) |
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ligand (chemical) gated channels |
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open by binding signaling molecule to a receptor associated w/ a channel (Ach to nicotinic receptor opens Na+ channel) |
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mechanically gated channel |
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respond to physical deformation (stretch) |
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intracellular messenger gated channel |
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binding of Ca2+, ATP, or cGMP to intracellular surface of a channel alters permeability |
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transporter/carrier proteins |
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bind ions/molecules on one side and undergo conformational change in order to transport molecule to opposite side of membrane; chemical specificity - structurally related molecules may compete for transport (competitive inhibition), cmpds not structurally related to transport substrate may bind to transporter in diff. area and change affinity of transporter for normal substance; rate of transport limited by time required to undergo conformational change; uniporters, symporters, antiporters/exchangers, ATP-dependent transporter, Ca2+ATPase, H+ and H+K+ATPase |
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bind/transport only one substance either with or against its energy gradient |
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binds 2 or more different substances on the same side of the membrane and transports all substances to opposite side of the membrane; usually involves one substance moving with and one against energy gradient (Na+glucose or Na+amino acid symporters = Na+ moves w/ gradient, both move into cell) |
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binds two different substances on opposite surfaces from each other and transports bound substances to other side of membrane; usually one with and one against energy gradient (Na+H+ or Na+Ca2+ exchangers - Na+ moves into cell w/ gradient and H+ or Ca2+ moves out of cell against gradient) |
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ATP-dependent transporter - ATPases |
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one or more substances bound and transported across membrane against energy gradient; Na+K+ATPase - most common, maintains normal cell volume/pressure/resting membrane potential, receptor site for 3 Na+ on inside (moves out of cell) 2 K+ on outside (moves into cell) (therefore electrogenic b/c net movement or 3 + ions out and 2 + in), high cellular energy expenditure; Ca2+ATPase - maintains low intracellular [Ca2+] by pumping Ca2+ out of cell or into intracellular storage areas; H+ and H+K+ATPases - present in kidney tubule/gut mucosa, facilitates acidification of urine/gastric contents |
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requires alteration of plasma membrane; allows transfer of contents b/w cellular compartments; consumes energy (breakdown of ATP/GTP); requires increase intracellular [Ca2+]; endocytosis, exocytosis, transcytosis |
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form of vesicular transport; infolding of membrane to allow large molecule to enter cell; phagocytosis, pinocytosis, receptor-mediated(regulated) endocytosis |
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form of endocytosis; "cell-eating"; ingestion/breakdown of very large molecules (bacteria, dead cells, particulate matter); occurs only in certain cells (tissue macrophages, leukocytes); often receptor-mediated |
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form of endocytosis; "cell-drinking"; non-specific uptake of small molecules/water; feature of endothelial cells lining blood vessels |
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receptor-mediated(regulated) endocytosis |
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form of endocytosis; triggered by binding of molecules to receptors; concentrated in clathrin(protein)-coated pits, then endocytosed and fused w/ lysosome; more specific and can occur more rapidly than constitutive endocytosis |
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form of vesicular transport; fusion of vesicle w/ plasma membrane to eject molecule from cell; used for movement of neurotransmitters and secretory proteins; can be constitutive (product made and immediately released) or regulated (product made and stored); involves interaction w/ SNARE protein and regulated by various cellular proteins |
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form of vesicular transport; endocytosis across one membrane and exocytosis across the opposite membrane (endocytosis/exocytosis coupling - maintains constant cell surface area) |
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mechanisms associated w/ movement of molecules through plasma membrane |
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actual movement of molecules; active transport, diffusion, osmosis |
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mechanism used to move molecules; requires energy source (therefore linked to cellular metabolism); movement of ions/substances across membrane in combo w/ pump (carrier protein) agrainst energy gradient; primary active, secondary active |
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form of active transport; energy for transporting molecules comes directly from hydrolysis of ATP (Na+K+ATPase) |
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secondary active transport |
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form of active transport; energy for transport provided indirectly by ATP hydrolysis; movement of one substance down its energy gradient is coupled w/ movement of another molecule against its gradient using carrier protein (Na+ driven symporters and antiporters); indirect use of ATP |
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mechanism used to move molecules; no cellular input of energy required; energy is provided by normal random thermal motion of atoms/molecules; reach equilibrium; movement is bi-directional (net movement results from - chemical gradient, electrical gradient, electrochemical gradient); simple and facilitated |
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form of diffusion; occurs through intermolecular spaces of membrane lipids or through channels/pores; no energy required |
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form of diffusion; requires use of carrier proteins |
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factors affecting net (directional) rate of diffusion across a membrane |
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fick's law of diffusion; permeability of a diffusing molecule |
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Fick's law of diffusion (know concept) |
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Definition
J = -D A (change c / change x) ; when no electrical or pressure differences, then the diffusion rate (molecules/sec) across a membrane is proportional to the area of the membrane and the difference in concentration of the diffusion substances on the 2 sides of the membrane; J = net diffusion rate, D = diffusion coefficient of the diffusing solute, A = surface area of membrane, change c = concentration difference, change x = membrane thickness |
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permeability of diffusing molecule |
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incorporates D, change x, and A (diffusing solute, membrane thickness, surface area, respectively); lipid solubility of molecule -> increased lipid solubility = increased J |
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mechanism used to move molecules; "diffusion of water"; net movement of water through selectively permeable membranes; caused by concentration differences across membranes (low permeability of solutes as compared to water); water moves from high to low concentration |
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amt of pressure exerted that is just sufficient to stop net movement of water (osmosis); depends on number of particles in solution |
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osmotic pressure generated by proteins in soln |
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based on total solute concentration; normal osmotic pressure of ECF and ICF is about 300 mOsm |
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solutes that are able to pass through membrane; cause only transient changes in cell volume - greater permeability of membrane to a permeant solute, more rapid the time course of the transient change |
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solutes not able to pass through membrane; concentration of impermeant solutes determines steady-state volume of cell |
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osmolarity of any given soln relative to plasma and how is affects cell volume |
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solns w/ same osmolarity as plasma; cells in isotonic soln will not change size - no net movement of water |
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solns w/ less osmolarity than plasma (low solute, high water); cells swell and may rupture - due to movement of water from higher concentration outside the cell to lower concentration inside the cell |
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solns w/ greater osmolarity than plasma (high solute, low water); cells shrink/crenulate - due to movement of water from high concentration inside the cell to low concentration outside the cell |
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non-isotonic cell volume regulation |
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occurs in certain regions of body where not isotonic (medulla of kidney) or when water balance altered; many cells have mechanisms that limit degree to which cell volume changes |
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if an ion or charged molecule cannot diffuse through the membrane, the distribution of permeable ions will be affected; non-permeant cellular proteins are trapped w/in the cell and tend to carry a net negative charge - tends to inhibit movement of cations out of cell but favors anions out, results in asymmetric distribution of permeable ions across membrane |
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provided by charged particles separated across a membrane so that ions will move (given a chance) even in the absence of a concentration difference; opposites attract and like repel |
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point at which forces produced by the concentration (chemical and electrical)gradients of a given ion across a membrane balance each other |
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Nernst equilibrium potential |
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determine equilibrium potential of any given ion but assumes free permeability; prediction; Eion = (-61.5/Z)log([ioni]/[iono]); units mV; Eion = equilibrium potential for given ion; z = valence and *charge*; [ioni] = concentration ion inside; [iono] = concentration ion outside |
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resting membrane potential |
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RMP; all cells = negative RMP = ICF negative in comparison to ECF; excitable cells have lower RMP than non-excitable; K= has most influence on RMP; results from: differences in permeability of membrane (conductance to K+ large = leakage out of cells, Gibbs-Donnan (proteins trapped w/in cell that influence ion distribution), electrogenic pump (Na+K+ATPase), Eion for a given ion (more permeant the ion, the greater its ability to force the membrane potential toward its equilibrium potential), Chord Conductance (Golmans) Equation, measured resmting potential more negative than potential predicted by Goldman (doesnt account for contribution of electrogenic pump to RMP ); RMP varies due to differential permeabilities of ions (avg of -70 mV... rang -9 to -90 mV); excitable cells |
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Chord Conductance/Goldmans Equation |
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Vm = EK+ +ENa+ + ECl-.... Vm = membrane potential, not equal to Eion; weighted avg of equilibrium potentials of all ions to which membrane is permeable esp. K+, Na+, Cl-; changes in ECF K+ alters RMP in all cells |
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nerve and muscle cells; more polar/-; contain voltage gates; reductions in membrane potential can trigger voltage-dependent increases in Na+ channel oppening and Na+ influx increases greatly; can initiate self-generation of electrical impulses |
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AP; rapid and large change in membrane potential followed by return to RMP; self-propagating electrical impulse; size and shape differ; voltage-gated channels in plasma membrane responsible for AP; *all-or-none response*; stimulus can be electrical, chemical, or mechanical - 2 physiochemical disturbances (sub-threshold/local response, threshold response) |
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sub-threshold/local response |
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non-propagated potentials - size of potential change decrease exponentially w/ distance from the site of disturbance; depolarizing stimulus - moves Vm closer to zero; hyperpolarizing stimulus - moves Vm further away from zero (less excitable) |
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generates action potential/nerve impulse; much larger in response, polarity of cell reverses; propagated w/out decrement - carried along whole length of cell w/out decrease in size/shape; supra-threshold stimulus doesn't increase size of AP |
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low threshold for excitation; 15-30 mV depolarization of RMP will initiate AP; RMP apprx -90 mV in spinal nerves/skeletal muscle/ventricular cardiac myocytes, -70 mV in most neurons of CNS, -60 to -40 mV in smooth muscle |
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AP duration of 4 ms; involves changes in conductance of Na+ and K+ ions via VG channels; AP initiated when threshold reached by larger intensity single stimulus, summation of smaller sub-threshold stimuli; depolarization, repolarization, hyperpolarization |
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15-30 mV change = opening of critical number of rapid activating VG Na+ channels; positive feedback mechanism (Na+ entry causes more Na+ gates to open until are open); Na+ entry pulls membrane potential to Na+ equilibrium potential; membrane depolarizes, then overshoots isoelectric point (inside becomes positive); Vm reaches about 50 mV b/c as membrane becomes more positive: Na+ gates inactivate, slow VG K+ channels open |
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rapid decrease in Na+ conductance and increase in K+ conductance returns the membrane potential toward resting level (prevents further entry of Na+ and K+ can leave); as membrane potential approaches RMP, slow K+ channels still open and fast Na+ channels closed |
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K+ channels slow to close, Vm pulled toward K+ equilibrium potential = more negative Vm than resting levels; slower phase; VG channels close and cellular pumps restore RMP |
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time in which another action potential cannot be generated at the same point in the membrane; absolute and relative |
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absolute refractory period |
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time from beginning of AP until repolarization is apprx 2/3 complete; no stimulus arriving during this period, no matter how large, can initiate another AP |
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relative refractory period |
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follows absolute refractory period and last until RMP reestablished; requires stronger stimulus to overcome hyperpolarizing effect of VG K+ channels that are still open in order to reach threshold and initiate new AP |
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propagation and conduction |
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Definition
AP is local response occurring at one specific area on membrane; inflow of + ions that occurs during depolarization are attracted to neighboring - charged areas of membrane (local current flow of + ions depolarizes membrane in neighboring area,; triggers opening of VG Na+ channels in area and threshold is reached); self-propagating (new AP is generated at neighboring area; domino-like effect); AP will not travel backwards (due to refractory period, must reset and await new stimulus); insulation prevents loss of current; fibers (axons) larger in diameter have faster conduction rate (due to lower resistance) |
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myelin (covering on axon due to 1.) Schwann cells (around nerves in PNS) - gaps b/w adjoining cells where AP occurs = Nodes of Ranvier; 2.) oligodendrocyte - around nerves in CNS); excellent insulator (prevents flow of ions b/w ECF and ICF except at nodes); increase velocity; conserves energy; prevents stimulation of neighboring axons; (unmyelinated = more energy to conduct AP) |
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functional unit of nervous system; soma/cell body; dendrites; axon |
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contains nucleus; Nissl bodies = stacks of rER; prominent Golgi; mitochondria (make neurotransmitters) |
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branching receptive end of neuron; more dendrites = more connections |
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exits from cell body and carries AP; one axon per cell body; axon hillock = usual site where AP generated due to high concentration of VG Na+ channels = lowest threshold for activation); may be myelinated; ends w/ spray of branches (terminal arborization) |
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branched end of axon containing: transmitter vesicles (packets of neurotransmitter surrounded by membrane), mitochondria (provide ATP for exocytosis of neurotransmitters and synthesis of new transmitters), VG Ca2+ channels (allow Ca2+ into cell which is required for exocytosis of neurotransmitter), pumps (to restore proper ion balance and to re-uptake unused neurotransmitter/precursor molecules, enzymes (to allow re-synthesis of neurotransmitters from precursor molecules) |
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place where electrical signal (AP) in one neuron is converted to a chemical signal in order to cross the space b/w the axonal terminal of one neuron and the receptive membrane of another neuron/effector tissue; synaptic cleft = physical gap across which neurotransmitters must diffuse; unidirectional (pre- and post-synaptic elements = axodendritic (axon terminal and dendrite), axosomatic (axon and soma), axoaxonic (axon and axon), neuromuscular junction (NMJ, axon and skeletal muscle) |
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post-synaptic (element) membrane |
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region called active zone contains: receptors (specific for neurotransmitter released), coupling mechanism/signal transduction pathway (means by which to change cellular response), catabolic enzymes (located on outer surface of membrane and acts to breakdown/inactive the neurotransmitter, prevents continual stimulation of post-synaptic cell...acetylcholinesterase) |
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general sequence of events @ chemical synapse |
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presynaptic neuron -> synaptic cleft -> post-synaptic membrane at skeletal muscle |
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contains neurotransmitter; AP travels down motor neuron to axon terminal; depolarization of axon terminal results in transient opening of VG Ca2+ channels located on plasma membrane; increased intracellular [Ca2+] and presence of ATP cause neurotransmitter vesicles to fuse w/ membrane @ synaptic cleft and empty (exocytosis) contents into synaptic cleft @ active zone (SNARE proteins and others involved); quantal (quantum = amt of Ach in one vesicle) release of neurotransmitter into synaptic cleft is proportional to intracellular [Ca2+]; increased intracellular [Ca2+] activates pumps (Na+Ca2+antiporter (secondary active) acts to remove Ca2+ from cytoplasm, Na+K+ATPase acts to restore RMP, re-uptake pumps bring in unused/degraded neurotransmitter/product back into cell- vesicle recycled); synthesis enzyme activated |
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neurotransmitter diffuses across cleft due to large concentration difference from release site (pre-synaptic terminal) to motor end plate (post-synaptic membrane); speed of conduction limited by time required to diffuse across cleft = synaptic delay |
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post-synaptic membrane @ skeletal muscle |
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neurotransmitter binds to specific membrane receptors (metabotropic and ionotropic); opening of ion channels; changes membrane potential of post-synaptic cell and excitability (neuron = EPSP or IPSP; skeletal muscle = EPP); degradation mechanism for neurotransmitter - degrades neurotransmitter preventing continual stimulation initiated by a single nerve impulse |
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excitatory post-synaptic potential (EPSP) |
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membrane potential change of a neuron = excites |
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inhibitory post-synaptic potential (IPSP) |
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membrane potential change of neuron = inhibits |
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end plate potential (EPP) |
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membrane potential change of skeletal muscle |
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