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Flashcards in Membranes and receptors 4 Deck (81)
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What is an action potential?

A momentary change in electrical potential across a membrane of a cell, especially of a nerve or muscle cell, that occurs when it is stimulated, resulting in the transmission of an electrical impulse. It occurs when a threshold level of depolarisation has been reached and therefore is an all or nothing state and can be propagated without loss of amplitude.


Stimulation of an action potential depends on what properties of the cell membrane and surrounding solution?

1. The relative permeability of the membrane
2. The ionic gradient across that membrane


What is the effect of reducing extracellular Na+ concentration on the equilibrium potential of sodium? What is that effect on the peak of an AP?

The equilibrium potential becomes more negative. Therefore the peak of the action potential also becomes increasingly negative (smaller peak).


Give the Nernst equation you would use to calculate the equilibrium constant for an ion:

E(i) = (61/Z) x log10 ([ion]o/[ion]i)


What happens to the membrane potential if the conductance for any particular ion is increased?

The membrane potential will move closer to the equilibrium potential of that ion.


What does the conductance of the membrane to a particular ion depend upon?

The number of channels for that ion that are open.


What happens to the conductance of sodium ions once the threshold of depolarisation has been reached and an action potential is triggered?

The conductance of Na+ rapidly increases as more and more Na+ channels open.


In general, what amount of ions need to flow to generate an action potential?

Only a small amount e.g. only ~ 0.4% increase in intracellular axon [Na+] occurs during an action potential


What is voltage-clamping? How does it enable you the investigated the mechanism of action potential generation?

Voltage clamping allows you to control membrane potential and therefore you can measure the currents flowing through the membrane at given membrane potentials. This gives a much clearer measurement of the effect of voltage on the number of Na+ and K+ channels open at different membrane potentials.


What is patch-clamping? How does it enable you the investigated the mechanism of action potential generation?

Patch clamping is a technique that enables currents flowing through individual ion channels to be measured. It allows you to investigate the time-frames of opening and closing of these ion channels during the action potential.


How does using different ionic concentrations enable you to investigate action potential generation?

It enables you to investigate the different contributions of different ions to the action potential.


What is the difference in the opening and closing of Na+ and K+ voltage-gated channels during an action potential?

Na+ channels opening increases rapidly and then decreases rapidly as they become inactivated. K+ channels open more slowly and close more slowly, therefore they do not close immediately upon repolarisation.


Describe the ion channels at the axon hillock. What is their purpose?

There is a high density of voltage-gated Na+ channels, enabling the triggering of action potentials.


What is the basis of the all or nothing characteristic of action potentials?

The positive feedback that occurs once depolarisation to threshold has happened. Beyond this membrane potential Na+ channels open, Na+ enters the cells and depolarises the membrane potential further, so more Na+ channels open.


What determines the threshold value of an action potential?

This is the membrane potential which opens up enough Na+ channels to overcome the hyperpolarising effect of the (non-voltage gated) K+ channels and therefore causes depolarisation which open up more Na+ channels (positive feedback occurs).


What happens during the upstroke of an action potential?

Depolarisation to threshold ->
1. Na+ channels open
2. Na+ enter the cell
3. Membrane depolarises
cycle begins again


What happens during the downstroke of an action potential?

Depolarisation causes ->
1. Voltage-gated K+ channels to open and inactivates Na+ channels
2. K+ efflux starts and Na+ influx stops
-> repolarisation


What is the role of the Na+-K+ pump in repolarisation of the action potential?

None! It just works in the background to maintain the Na+/K+ gradient.


What is meant by the absolute refractory period?

The period when nearly all Na+ channels are in their inactivated state. Therefore it does not matter how much stimulus is now being received a new action potential will not be generated as there are not enough Na+ channels able to open.


What is meant by the relative refractory period?

Na+ channels are recovering from inactivation, the excitability returns towards normal as the number of channels in the inactivated state decreases. Therefore a new action potential can be triggered in this period.


What is accommodation?

It is a state that occurs after a membrane experiences a long period of stimulus. This causes an increasing number of Na+ channels to be in their inactivated state and consequently a larger depolarisation of the membrane becomes necessary to trigger an action potential (the threshold potential becomes more positive).


What happens to the peak of an action potential when the membrane becomes increasingly accommodated?

Peak decreases in amplitude because there are less Na+ channels available to open and therefore a smaller influx of Na+ into the cell.


How would accommodation occur physiologically?

In an axon which has received prolonged stimuli from excitatory neurotransmitters but none that have depolarised the axon hillock enough to cause an action potential.


What is the basic structure of voltage-gated Na+ channels?

1. 6 transmembrane domains, repeated 4 times
2. Form a functional channel with a pore in the middle


What is the function of transmembrane domain 4 in voltage-gated Na+ channels?

It contains positively charged amino acids which lie in the membrane and detect the voltage field. It causes a voltage-dependent conformation change which opens the pore.


What is the function of the pore/ H5 region?

It is a strip of amino acids which form a beta-sheet that dips into the membrane and contributes to the pore selectivity.


What is the function of the inactivation particle?

It is a region of the channel which covers the pore of the channel when it is in its inactive state.


What is the difference in structure between a Na+ voltage-gated channel and a K+ voltage-gated channel?

Na+ channel is a monomer whereas K+ channel is a tetramer, however each K+ monomer contains the same 6 transmembrane structure as the Na+ repeat unit.


How does patch clamping work?

You touch the membrane, creating a seal around the glass pipette and therefore can measure the current passing though that small part of the membrane which is hopefully just one channel.


How in general do local anaesthetics, such as procaine, work?

All local anaesthetics are membrane stabilizing drugs; they reversibly decrease the rate of depolarization and repolarization of excitable membranes (like nociceptors). Local anesthetic drugs act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, in particular the voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel.