Session 5.1: Ionic mechanisms of action potential Flashcards

1
Q

what is action potential

A

change in membrane potential

depends on ionic gradient and relative permeability of membrane

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2
Q

what are some key features of action potential

A

only occurs if threshold level reached
all or nothing
propagated along axon without loss amplitude

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3
Q

what is action potential for axon like

A

reaches +30

lasts 0.5ms

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4
Q

what is action potential of skeletal muscle like

A

reaches +40

lasts 0.5ms

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5
Q

what is action potential of sino-atrial node like

A

reaches +30

lasts 100ms

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6
Q

what is action potential of cardiac ventricle like

A

reaches +30

lasts 100ms

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7
Q

what is the conductance of the membrane dependent on

A

the number of channels for that particular ion that are open

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8
Q

if the conductance(g) of an ion is increase

A

the membrane potential (Vm) will move closer to equilibrium potential (EION) of that ion

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9
Q

even if small amount of ions move

A

relatively large change in membrane potential formed

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10
Q

as axon diameter increases from 1->5->10

A

increase in sodium required to produce 100mV depolarisation 50 microM -> 8 -> 4 required

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11
Q

why does sodium move into the cell

A

due to concentration and electrical gradient

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12
Q

what happens when open sodium channels

A

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

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13
Q

why does the membrane not reach the sodium equilibrium potential

A

as other ions present on membrane

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14
Q

what is concentration gradient for potassium

A

wants to move out

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15
Q

what is electrochemical gradient for potassium

A

want to move in

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16
Q

in what direction does potassium move when potassium channels are open

A

the chemical gradient exceeds the electrical gradient for potassium, so potassium moves out

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17
Q

why does potassium move out of the cell

A

to bring membrane potential closer to potassium equilibrium potential

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18
Q

what would happen if the equilibrium potential was reached for potassium

A

the electrical and chemical gradient for potassium would be equal but opposite
so no electrochemical gradient

19
Q

how do we show experimentally that the sodium ion concentration is responsible for AP depolarisation

A

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

20
Q

why does action potential over shoot

A

action potential is trying to reach the sodium equilibrium potential

21
Q

how are membrane currents measured at a set membrane potential

A

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

22
Q

what would happen to membrane potential is sodium conductance changes

A

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

23
Q

what would happen to membrane potential if potassium conductance changes

A

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

24
Q

how is resting potential reaches

A

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

25
Q

what is the trigger to generate action potential

A

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

26
Q

action potential =

A

increase sodium conductance

27
Q

what happens to channel activity during axonal action potential

A

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

28
Q

is the sodium/potassium ATPase important

A

not involved in repolarisation of action potential as no changes in the concentrations of ions

29
Q

how are sodium ions activated from deactivated state

A

hyperpolarisation - necessary for recobery

30
Q

what is the absolute refractory period

A

for recovery

will not initiate another action potential - all sodium channels inactivated

31
Q

what is the relative refractory period

A

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

32
Q

what are key features of structure of voltage gated sodium channel

A

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
33
Q

what is the basic structure of a voltage gated sodium channe

A

spherical sodium channel with pore in the middle

34
Q

what is the structure of the voltage gated potassium channels

A

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

35
Q

how to measure currents through individual ion channels

A

patch clamping - isolate small piece of membrane and measure current

36
Q

when do sodium channels open

A

all open close to voltage pulse
-80 = closed
-30 = change, conformational, open
then blocked until back to closed state

37
Q

what are two forms of local anaesthetics

A

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)

38
Q

what is an example of a local anaesthetic

A

lidocaine
if unprotonated = lipophilic (membrane permeable)
if protonated = hydrophhilic (membrane impermeable)

39
Q

what is local anaesthetic used for

A

treat cardiac arrhythmias

40
Q

how do local anaesthetic work

A

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

41
Q

what does the importance 0f hydrophobic and hydropgilic pathways vary on

A

the lipid solubility of the drug

42
Q

in what order does local anaesthetic block

A
  1. small myelinated axons
  2. unmyelinated axons
  3. large myelinated axons
43
Q

why is it important that sodium ion channels become inactivated

A

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

44
Q

what are the consequences of the delayed closing of voltage gated potassium channels

A

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