Session 5.1: Ionic mechanisms of action potential

Question 1

what is action potential

Answer 1

change in membrane potential

depends on ionic gradient and relative permeability of membrane

Question 2

what are some key features of action potential

Answer 2

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

Question 3

what is action potential for axon like

Answer 3

reaches +30

lasts 0.5ms

Question 4

what is action potential of skeletal muscle like

Answer 4

reaches +40

lasts 0.5ms

Question 5

what is action potential of sino-atrial node like

Answer 5

reaches +30

lasts 100ms

Question 6

what is action potential of cardiac ventricle like

Answer 6

reaches +30

lasts 100ms

Question 7

what is the conductance of the membrane dependent on

Answer 7

the number of channels for that particular ion that are open

Question 8

if the conductance(g) of an ion is increase

Answer 8

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

Question 9

even if small amount of ions move

Answer 9

relatively large change in membrane potential formed

Question 10

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

Answer 10

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

Question 11

why does sodium move into the cell

Answer 11

due to concentration and electrical gradient

Question 12

what happens when open sodium channels

Answer 12

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

Question 13

why does the membrane not reach the sodium equilibrium potential

Answer 13

as other ions present on membrane

Question 14

what is concentration gradient for potassium

Answer 14

wants to move out

Question 15

what is electrochemical gradient for potassium

Answer 15

want to move in

Question 16

in what direction does potassium move when potassium channels are open

Answer 16

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

Question 17

why does potassium move out of the cell

Answer 17

to bring membrane potential closer to potassium equilibrium potential

Question 18

what would happen if the equilibrium potential was reached for potassium

Answer 18

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

Question 19

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

Answer 19

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

Question 20

why does action potential over shoot

Answer 20

action potential is trying to reach the sodium equilibrium potential

Question 21

how are membrane currents measured at a set membrane potential

Answer 21

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

Question 22

what would happen to membrane potential is sodium conductance changes

Answer 22

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

Question 23

what would happen to membrane potential if potassium conductance changes

Answer 23

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

Question 24

how is resting potential reaches

Answer 24

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

Question 25

what is the trigger to generate action potential

Answer 25

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

Question 26

action potential =

Answer 26

increase sodium conductance

Question 27

what happens to channel activity during axonal action potential

Answer 27

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

Question 28

is the sodium/potassium ATPase important

Answer 28

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

Question 29

how are sodium ions activated from deactivated state

Answer 29

hyperpolarisation - necessary for recobery

Question 30

what is the absolute refractory period

Answer 30

for recovery | will not initiate another action potential - all sodium channels inactivated

Question 31

what is the relative refractory period

Answer 31

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

Question 32

what are key features of structure of voltage gated sodium channel

Answer 32

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

Question 33

what is the basic structure of a voltage gated sodium channe

Answer 33

spherical sodium channel with pore in the middle

Question 34

what is the structure of the voltage gated potassium channels

Answer 34

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

Question 35

how to measure currents through individual ion channels

Answer 35

patch clamping - isolate small piece of membrane and measure current

Question 36

when do sodium channels open

Answer 36

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

Question 37

what are two forms of local anaesthetics

Answer 37

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)

Question 38

what is an example of a local anaesthetic

Answer 38

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

Question 39

what is local anaesthetic used for

Answer 39

treat cardiac arrhythmias

Question 40

how do local anaesthetic work

Answer 40

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

Question 41

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

Answer 41

the lipid solubility of the drug

Question 42

in what order does local anaesthetic block

Answer 42

1. small myelinated axons 2. unmyelinated axons 3. large myelinated axons

Question 43

why is it important that sodium ion channels become inactivated

Answer 43

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

Question 44

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

Answer 44

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