• differences in membrane permeability
• the types of channels, transporters, pumps present in a given cell that determine cell fxn

measure of a solute's permeability through a membrane

σ = 0 highly permeable

↓

σ = 1 impermeable

• highly permeable to small uncharged molecules
• if small enough, polar molecules can also pass

• Larger uncharged and/or polar molecules
• Ions

Simple Diffusion:

define, rate factors, characteristics, examples

• moving down a concentration gradient
• rate depends on lipid solubility
• can use channels
• does not require energy
• no Vmax
• aquaporins for water, gated channels for ions

diffusion down a concentration gradient

relies on carriers

does NOT require energy

does have a Vmax

often a uniporter that transports specific substance

• concentration gradient
• electrical gradient
• hydraulic pressure

J = (PA/Δx) (C_A-C_B)

J= net rate of diffusion (flux)

P = permeability

A = area of membrane

C = conc diff across membrane

Δx = membrane thickness

• lipid solubility
• size/shape of diffusing molecule
• temperature
• membrane thickness

can be simple or complex

(open/closed or inactivated)

pass selective ions across the membrane

Voltage-Gated Channels

define, example, how does lidocaine affect?

• channel regulated by voltage, always in membrane
• Na⁺ or K⁺ channels for action potential
• blocks voltage gated Na⁺ channels to prevent occurence of nerve action potentials

ENaC:

define, location, fxn

• epithelial sodium channels in kidney, lung, and gut
• usually in apical membrane to provide pore for Na⁺ diffusion
• not always in the membrane - rely on aldosterone hormone to regulate presence

• Amiloride (hypertension drug) blocks ENaC to cause diuresis
• Liddle's Syndrome - ENaC mutation where channels are always open, causes hypertension

carrier protein brings substrate into cell

requires energy

ex: Na⁺/K⁺ ATPase - brings K⁺ in and pumps Na⁺ out, requires much of the cell's energy

is electrogenic, but contributes <10% of total membrane potential

What does ouabain do?

What drug is it found in?

• glycoside that inhibits the Na⁺/K⁺ ATPase
• ion gradient ↓ →Na-Ca pump ↓ → intracellular Ca2+ ↑
  
• as Na⁺ is leaking into the cell it brings water with it and can cause swelling and eventual bursting
• digoxin for a-fib or atrial flutter

What causes K⁺ to leak out of cell?

What causes Na⁺ to leak in?

K⁺ leaks out due to concentration gradient

Na⁺ leaks in due to electrical and concentration gradients

• membrane potential for movement of molecules across membrane or for action potential
• sodium concentration plays hugely important role in specialized co-transporters for other molecules

• ATP dependent pump moving ions across membrane against their concentration gradient
• ex: Ca²⁺ATPase - pumps Ca²⁺ out of cytoplasm after a Ca²⁺ triggered event

Secondary Active Transport:

define, two types, energy source

• uses driving force of one ion's concentration gradient to cotransport a second molecule
• Cotransport/Symport
• Countertransport/Antiport/Exchanger
• both molecules must be present for transporter to fxn
• does NOT require ATP

If Na-K pump inhibited, gradients ↓,     intracellular Ca²⁺ ↑

ex: digoxin (ouabain)

If Na-K pump runs faster due to ↑ gradients, intracellular Ca²⁺ ↓

ex: extracellular K⁺ builds up during exercise→Na-K pump turns faster→Na-Ca pump faster→more Ca²⁺ outside to ↑ bloodflow to muscle

(both of these rxns happen b/c the speed of the Na-Ca pump depends on the concentration gradient, which is affected by Na-K pump)

in epithelial cells

Apical - lumen/epithelial

Basolateral - lumen/blood

• excess excretion of dilute urine since water cannot be brought accross membrane
• central cause - insufficient ADH
• nephrogenic cause - mutations of ADH receptor or aquaporin-2

• follows solutes or flows through aquaporins
• NEVER actively transported (though ATP is used to place aquaporins in membrane)

Cystic Fibrosis:

effects on airway epithelia and sweat glands

Airway epithelia: CFTR (CF Transmembrane conductance Regulator) transports Cl^- out of cell, and Na⁺ and water follow paracellularly, which thins mucus

W/o CFTR, Cl^- is not secreted, mucus thickens and fosters bacterial growth

Sweat glands -  sweat is usually hypotonic since Na⁺ and Cl^- are reabsorbed, but with CF, Cl^- channels are defective and NaCl is lost in the sweat → electrolyte depletion

• Concentration of osmotically active particles

(1M NaCl→ 2 osmoles, 1M CaCl₂→ 3 osmoles)

• size/type of particle does not matter, only concentration
• water moves down gradient until osmolarities are equal

• isosmotic - very little movement of fluid
• hyperosmotic-water leaves cells→ cells shrink
• hyposmotic - water enters cells → cells swell

regardless of solution osmolarity, NaCl will never cross the membrane, water will regulate the osmolarity

osmolarity - defining # of particles per L

tonicity - describing whether cell swells or shrinks based on osmotic pressure from particles

↑↑ Na+ concentration

water loss, excess Na+

cells shrink

shrinking can cause vessels to tear, hemorrhage, profound effects on brain

↓↓ Na+ concentration

water excess, Na+ loss

cells swell

rapid swelling of cells can cause herniation which has profound effects on brain