Topic 1.4: Foundations - Biological basis of membrane potential

purpose of membrane

to separate intracellular environment from extracellular environment

achieved through hydrophobic/ hydrophilic interactions, simple diffusion and facilitated diffusion

cause of uneven distribution of K+ and Na+

presence of Na+/K+ ATPase in cellular membrane

active transport of Na+ and K+ against their individual concentration gradients

permeability of membrane to K+ and Na+

membrane is ~40x more permeable to k+ than Na+ → relatively large umber of potassium leak channels in cell membrane

K+ leak channels

specific to K+ so accompanying anion cannot follow K+ into extracellular space → results in negative membrane potential

bidrectional but uneven distribution results in higher net efflux than influx of K+

leak channel - def

channel that is always open -> whatever it carries can constantly leak in or out of the cell

Voltage gated ion channel - def

channel whose open or closed state depends on the value (polarity) of membrane potential

Ligand gated ion channels (receptor mediated ion channels) - def

ligand binding to a receptor opens the channel

Mechano-gated ion channels - def

mechanical stimulus opens or closes the channel

Mechano-gated ion channels - examples (4)

• stretch receptors

• touch receptors

• baroreceptors (stretch receptors that measure blood pressure)

• proprioceptors (sensory receptors that provide feedback to the body info about movement of limbs in space)

resting membrane potential - def and units

charge difference across the membrane when the membrane is at rest due to cations leaving the cell

ie. when permeability of cell is due entirely to leak channels -> no gated channels are open

units = mV (millivolts)

resting membrane potential and permeability to K+

The more permeable the membrane is to K+, the more negative the resting membrane potential will be

higher net efflux of K+ and inability of accompanying anions to follow through leak channels results in more negative resting membrane potential

depolarisation - def

increase in membrane potential towards and above 0mV

repolarisation - def

fall in membrane potential towards RMP

hyperpolarisation - def

fall in membrane potential lower than RMP -> due to excess efflux of K+ from the cell

potential energy drivers of ion movement across cellular membrane - list (2)

1. chemical concentration gradient

2. electrical charge difference

when both sources balanced → net movement of ion = zero and ion is in equilibrium

equilibrium potential of ions - summary (3)

also called nearnst potential

each ion will move across membrane in direction that brings membrane potential closer to ion’s own equilibrium potential

differs for each ion

effect of cation movement on membrane potential (2)

Cations entering cell = depolarise membrane

Cations leaving cell = hyperpolarise membrane

reversal potential - def

sum of impact of concentration gradient and electrical change difference across the membrane

reversal potential and ion flow (inflow and outflow)

When membrane permeability to K+ increases, reversal potential of potassium (E_K) is at more negative potential than RMP -> hyperpolarisation

At a normal resting potential of -65 mV, V_M > E_K → potassium flows out of the cell because the membrane potential is higher than the potassium reversal potential.

If the cell hyperpolarises to -90 mV, V_M < E_K → membrane potential drops below the potassium reversal potential, and potassium ions flow into the cell.

prediction if reversal potential of a particualr ion and membrane potential at the time is known (2)

which way the ion moves and roughly how fast it will be

nearnst equation - summary

predicts equilibrium potential of any ion given charge on ion and concentration gradient of ion on either side of the membrane

Measures point at which net movement of ion across membrane is zero

E_K - summary

typically more negative than the resting membrane potential.

if the conductance across the membrane for K⁺ increases, K⁺ will leave the cell and the membrane will hyperpolarise

E_Na - summary

typically more positive than the resting membrane potential

increasing conductance for Na⁺ will result in Na⁺ entering  the cell, depolarising the membrane.

driving force - summary (4)

sum of all forces on a particular ion, either pushing or pulling the movement of the ion

DF = V_m -E_ion

The nicotinic acetylcholine (nACh) receptor is an ionotropic receptor.

This means when a ligand binds to the receptor, it opens an ion channel.

The nACh is a monovalent cation channel.

Typically, the nACh depolarizes the membrane when activated.

This is because:

The resting membrane potential is further away from the E_Na than from the E_K.

The driving force on Na⁺ is higher than for K⁺.

Why is the reversal potential for Cl⁻ (ECl) close to resting membrane potential but significantly positive compared to the reversal potential for K+ (EK)

The presence of the Na/K ATPase pump but the absence of a Cl⁻ pump.

Why does increasing membrane permeability to K⁺ hyperpolarize the membrane?

The reversal potential of potassium (EK) is at a more negative potential than RMP.

The resting membrane potential is at roughly the ECl. Based on your understanding of the cell membrane can you propose a reason why?

The cell membrane has a high chloride permeability at rest and chloride channels remain open

results in the chloride concentration matching the membrane resting potential.

opening of Na+ selective ion channel on membrane potential

ion flows through channel to increase membrane potential as E_Na is more positive

membrane depolarisation

opening of K+ selective ion channel on membrane potential

ion flows through channel to decrease membrane potential as E_K is more negative

membrane hyperpolarisation

Goldman Hodgkin Katz equation - summary

predicts membrane potential given the distribution of ions across the cell membrane and the permeability of the membrane to that ion

Excludes consideration of Ca2+ -> intracellular and extracellular concentration of calcium ions are small relative to the other ions

membrane permeability to Na+ during action potential

10,000x more permeable compared to at rest

when would the Goldman Hodgkin Katz equation predict no net flow of ions

membrane potential = specific equilibrium potential of ion

ie. when chemical concentration gradient and electrical charge different balance