2.3 - Membrane Potentials and Action Potentials Flashcards
What is diffusion and ion flux?
- diffusion: the movement of ions from area of high concentration to area of low concentration down a concentration gradient in order to reach a dynamic equilibrium
- spontaneous and no energy input required
- useful for transport over small distances
- ion flux: the number of ions that cross a unit area of membrane per unit time i.e. molecules.m^-2.s^-1
- flux is generated by the opening / closing of ion channels, affecting ion flow
Electrical properties of excitable cells
- voltage / potential difference (volts) - generated by ions to produce a charge gradient (i.e. like a chemical battery)
- current (amps) - movement of ions due to a potential difference
- resistance (ohms) - barrier that prevents the movement of ions
- voltage = current x resistance
- closed ion channels = high resistance
- open ion channels = low resistance
How do you measure membrane potential?
- all cells have a membrane potential - the difference in voltage between inside and outside
- to measure this, a reference electrode is placed outside the cell - this is the zero-volt level
- another electrode is placed inside the cell - it measures a voltage that is negative compared with the outside
Why are ion channels needed?
- lipid (hydrophobic) cell membranes are barriers to ion movement and separate ionic environments
- the cell membrane can selectively change its permeability to specific ions
- permeable pores in the membrane (ion channels) open and close depending on transmembrane voltage, presence of activating ligands or mechanical forces
- ion channels can be selective for different types of ion e.g. K+, Na+, Cl-, Ca2+
- movement across the membrane will occur when the ion concentration is different on one side of the membrane and will stop when equilibrium is reached
What happens when compartment 1 (with 0.15M NaCl) and compartment 2 (with 0.15M KCl) are separated by a membrane with no channels?
- if there are no channels present in the membrane, there is no diffusion across the membrane despite the concentration gradients
- there is no separation of charge
- membrane potential = 0 mV
What happens when compartment 1 (with 0.15M NaCl) and compartment 2 (with 0.15M KCl) are separated by a membrane that is only permeable to K+?
- K+ crosses the membrane and the direction of flux is dictated by its concentration gradient (there is 0.15M K+ in C2 and 0M K+ in C1 –> C2 to C1)
- charge separation between compartments occurs as C1 gains +ve charge (K+) and C2 becomes more -ve (loss of K+)
- the accumulation of +ve charge in C1 prevents further influx of K+ into C1, and even repels some K+ back into C2 - equilibrium reached as +ve charge in C1 balances concentration gradient pushing K+ from C2–>C1
- this is the state of electrochemical equilibrium - electrical forces (electrical gradient) balance diffusion forces (concentration gradient)
- a stable transmembrane potential is achieved
- same case if membrane is only permeable to Na+, but vice versa and the membrane potential has the opposite sign
What is equilibrium potential?
- the potential at which electrochemical equilibrium has been reached
- the potential that prevents diffusion of the ion down its concentration gradient
What is the Nernst equation?
- the equilibrium potential (= membrane potential) can be calculated using the Nernst equation, if you know the concentration of the ion on both sides
- E = (RT/zF)ln(X2/X1) where:
- R = gas constant
- T = temperature (K) - assume 37oC = 310 K
- z = charge on ion (e.g. +1, -1, +2)
- F = Faraday’s number - charge per mol of ion
- X2 = intracellular ion concentration
- X1 = extracellular ion concentration
Composition of the main fluid compartments
- Na+ and K+ are most important ions determining the resting potential of neurons
- Na+ - intracellular 15mM, extracellular 150mM
- K+ - intracellular 150mM, extracellular 5mM
- E (K+) = -90 mV
- E (Na+) = +72 mV
What is the Goldman-Hodgkin-Katz (GHK) equation and why is it needed?
- EK and ENa are theoretical values - in reality biological membranes are not uniquely selective for an ion
- membranes have mixed and variable permeability to all ions (but for neurones at rest K+»_space; Na+ etc)
- a typical resting membrane potential (Em) is -70 mV not -90 mV (which is Ek)
- each ion’s contribution to membrane potential is proportional to how permeable the membrane is to the ion at any time
- the GHK equation describes the membrane potential more accurately:
- P - permeability / channel open probability (0 = 100% closed, 1 = 100% open, 0.5 = open 50% of time)
- subscript on P indicates ion
- [] = concentration in moles
- subscript i or o indicates inside / outside cell
- the equation takes into account relative permeabilities and concentration gradients of different ions
- Em (mV) = -61 * log((Pk[K]i + PNa[Na]i + PCl[Cl]o)/(Pk[K]o + PNa[Na]o + PCl[Cl]i))
Worked examples of the GHK equation
- all channels are open all the time (Pk=1, PNa=1, PCl=1)
- Em = -14 mV - K+ channels open, Cl- and Na+ channels closed (Pk=1, PNa=0, PCl=0)
- Em = -90 mV - now increase Na+ permeability by 5% (Pk=1, PNa=0.05, PCl=0)
- Em = -66 mV
- close to actual value, since at rest the membrane is permeable to K+ but also has a finite permeability to some Na+ which makes membrane potential more positive
Changes in membrane potential - definitions
- depolarisation - membrane potential becomes more positive towards 0mV
- repolarisation - membrane potential decreases towards resting potential
- overshoot - membrane potential becomes more positive than 0mV
- hyperpolarisation - membrane potential decreases beyond resting potential
What are graded potentials?
- change in membrane potential in response to external stimulation or neurotransmitters
- change in membrane potential is graded in response to the type or strength of stimulation - e.g. stimulus may produce depolarisation or hyperpolarisation (more K+ channels open = -ve)
- weak stimuli produce small depolarisation, strong stimuli produce large depolarisation
- graded potentials produce the initial change in Em that determines what happens next - initiate/prevent action potentials
- graded potentials decay along the length of the axon due to charge leaking from the axon - size of potential change decreases over distance
What happens if the graded potential reaches a threshold?
- action potentials (AP) occur when a graded potential reaches a threshold for the activation (opening) of Na+ channels resulting in an ‘all-or-nothing’ event
- AP travels along the length of the axon
- they occur in excitable cells - mainly neurons and muscle cells but also in some endocrine tissues
- in neurons they are also known as nerve impulses and allow the transmission of information reliably and quickly over long distances
- play a central role in cell-to-cell communication and can be used to activate intracellular responses
- if threshold not reached, the response is graded and decays
What is the ionic basis of action potentials?
- permeability of membrane depends on conformational state of ion channels:
- opened by membrane depolarisation
- inactivated by sustained depolarisation
- closed by membrane hyperpolarisation/repolarisation
- when membrane permeability of an ion increases, it crosses the membrane down its electrochemical gradient
- this movement changes the membrane potential towards the equilibrium potential for that ion
- changes in membrane potential during the AP are not due to ion pumps - these maintain concentration gradient but do not change membrane potential (Em changes caused by flow of ions through ion channels)