Session 5.1: Ionic mechanisms of action potential Flashcards
what is action potential
change in membrane potential
depends on ionic gradient and relative permeability of membrane
what are some key features of action potential
only occurs if threshold level reached
all or nothing
propagated along axon without loss amplitude
what is action potential for axon like
reaches +30
lasts 0.5ms
what is action potential of skeletal muscle like
reaches +40
lasts 0.5ms
what is action potential of sino-atrial node like
reaches +30
lasts 100ms
what is action potential of cardiac ventricle like
reaches +30
lasts 100ms
what is the conductance of the membrane dependent on
the number of channels for that particular ion that are open
if the conductance(g) of an ion is increase
the membrane potential (Vm) will move closer to equilibrium potential (EION) of that ion
even if small amount of ions move
relatively large change in membrane potential formed
as axon diameter increases from 1->5->10
increase in sodium required to produce 100mV depolarisation 50 microM -> 8 -> 4 required
why does sodium move into the cell
due to concentration and electrical gradient
what happens when open sodium channels
membrane potential tries to reach sodium equilibrium potential - increasingly more positive (so Vm closer to Ena). then concentration gradient hasn’t changed much as not require much to depolarise membrane but electrical gradient changed direction, positive on inside, which repels and now puts positive ions out
why does the membrane not reach the sodium equilibrium potential
as other ions present on membrane
what is concentration gradient for potassium
wants to move out
what is electrochemical gradient for potassium
want to move in
in what direction does potassium move when potassium channels are open
the chemical gradient exceeds the electrical gradient for potassium, so potassium moves out
why does potassium move out of the cell
to bring membrane potential closer to potassium equilibrium potential
what would happen if the equilibrium potential was reached for potassium
the electrical and chemical gradient for potassium would be equal but opposite
so no electrochemical gradient
how do we show experimentally that the sodium ion concentration is responsible for AP depolarisation
if reduce extracellular sodium concentration then the amplitudes of action potential decreases
the peak of the action potential changes in a manner parallel to the changes in equilibrium potential of sodium
so upstroke of action potential is due to a large increase in permeability of sodium ions
why does action potential over shoot
action potential is trying to reach the sodium equilibrium potential
how are membrane currents measured at a set membrane potential
voltage clamp
control membrane potential and measure current
measures sodium current so if increases from -70 to +10 (then controlled at that level), the current shows an influx of sodium ion which causes depolarisation (downwards) - maintain depolarisation but then return to 0 due to inactivation of sodium channels. wheras potassium out and potassium current increases at depolarisation, but increases more slowly than sodium, potassium ion channels remain open, close once reach resting
what would happen to membrane potential is sodium conductance changes
no of sodium ion channels open increases with increased conductance and membrane potential increases. then inactivated. the peak of sodium equilibrium potential is near peak of membrane potential
what would happen to membrane potential if potassium conductance changes
no of potassium ion channels open increases with increased conductance, but more slowly and the conductance remains high for a longer time after. membrane potential decreases to try and reach potassium equilibrium potential
how is resting potential reaches
as potassium ion channels remain open so after overshooting it to too negative, increases it back up when these potassium ion channels then close. as very high potassium conductance at rest
what is the trigger to generate action potential
to reach a threshold in order to produce an action potential
action potential initated in nerve cell at axon hillock
- nerve cell make connective with dendrite and release neurotransmitter which attached to ligand gated ion channel causing:
1. small EPSP (depolarisation), but not reach threshold
2. an IPSP - inhibitory
3. large ESPS which reaches threshold, action potential initiated in axon hillock which will travel along axon
action potential =
increase sodium conductance
what happens to channel activity during axonal action potential
POSITIVE FEEDBACK
depolarises threshold - opened enough voltage gated sodium channels, so influx of sodium, causing depolarisation, which causes even more sodium channels to open
as membrane potential depolarises, sodium channels inactivate which will stop sodium influx, and depolarisation will cause opening of voltage gated potassium ion channels, so sodium influx stops, potassium effluxes and membrane repolarises
is the sodium/potassium ATPase important
not involved in repolarisation of action potential as no changes in the concentrations of ions
how are sodium ions activated from deactivated state
hyperpolarisation - necessary for recobery
what is the absolute refractory period
for recovery
will not initiate another action potential - all sodium channels inactivated
what is the relative refractory period
for recovery
can inititiate another action potential if nerve given strong enough stimulus…returning excitability of nerve back as sodium ion channels are recovering and start to become activated and the voltage gated potassium ion channels close
what are key features of structure of voltage gated sodium channel
voltage gated sodium channel:
- a functional sodium ion channel comprises only one alpha subunit which consists of four equal parts (repeats 1, 2, 3 and 4)
- each repeat has 6 transmembrane segment spanning = alpha helix, each 4th transmembrane contain a lot of positively charged amino acids which can experience an electrical field, so if membrane potential changes, the 4th will detect this and causes a change in conformation of sodium channel and so open…depolarisation
- there is a link between the 3rd and 4th repeat contains inactivation particle, enters pore and blocks it. mutations to inactivation particle can remove the inactivation of sodium channels
what is the basic structure of a voltage gated sodium channe
spherical sodium channel with pore in the middle
what is the structure of the voltage gated potassium channels
each voltage gated channel consists of 4 individual alpha subunit (alpha 1, 2, 3 and 4)
they have no inactivation particle
they have one repeat with a 4th transmembrane segment which contains amino acids which detect membrane voltage field ( one repeat per alpha subunit)
pore region (amino acid sequence of pore region determines its selectivity), allows potassium through pore
how to measure currents through individual ion channels
patch clamping - isolate small piece of membrane and measure current
when do sodium channels open
all open close to voltage pulse
-80 = closed
-30 = change, conformational, open
then blocked until back to closed state
what are two forms of local anaesthetics
can be protonated or unprotonated (charged or uncharged)
uncharged = membrane permeable
(1/4 in uncharged form at pH7.2, mostly uncharged as more protons to bind to anaestetics)
what is an example of a local anaesthetic
lidocaine
if unprotonated = lipophilic (membrane permeable)
if protonated = hydrophhilic (membrane impermeable)
what is local anaesthetic used for
treat cardiac arrhythmias
how do local anaesthetic work
block sodium channels - tends to block channels in open state - so if pain on pain fibres, channels open and more easily blocked
uncharged - pass through and along membrane
charged - cannot pass membrane but can enter channels
works by hydrophilic pathway (charge form) - open channel block stops sodium entering
or works by hydrophobic block pathway - uncharged form can cross through channel into pore and cause block
the local anasthetic (charged form) usually unblocks from channel when channel is in closed state
when in inactivated form - block of channel more stable
what does the importance 0f hydrophobic and hydropgilic pathways vary on
the lipid solubility of the drug
in what order does local anaesthetic block
- small myelinated axons
- unmyelinated axons
- large myelinated axons
why is it important that sodium ion channels become inactivated
to allow the rapid switch off of action potential, to enable repolarisation to occur quickly. and to allow them to recover so refractory period can occur which enables the action potential to travel in one direction
what are the consequences of the delayed closing of voltage gated potassium channels
ensures hyperpolarisation reaches a fairly negative value to allow for recovery from inactivation of sodium channels. the more the hyperpolarised -> the quicker the sodium channels will recover
