Lodish 4th edition: Chapter 21 pages 921 - 924
Moyes and Schulte: Chapter 5 pages 146-164
- passive conduction of a signal in a nerve is limited by the properties of
- not very efficient if need to have signal travel quickly over a long distance
- signal is reduced over distance
- active conduction (i.e. generating an action potential) means signal travels along nerve with NO loss of amplitude
Action potentials in neurons are mostly based on the voltage-gated Na+ channel, some neurons use both the voltage-gated Na+ channel and a voltage-gated K+ channel, some neurons use only the voltage-gated Na+ channel and some neurons use the voltage-gated Ca+2 channel
We will use the classic example of an action potential from the giant axon of the squid (invertebrate), also the action potential found in non-myelinated axons of mammals. This action potential has two components: voltage-gated Na+ channels and voltage-gated K+ channels
Voltage gated Na+ channel:
The channel has three states, closed, open and inactive.
Closed to Open: Depolarization is necessary to open the channel and therefore it acts to activate itself in a regenerative cycle. More Na+ influx depolarizes the membrane which opens more channels which depolarizes the membrane more.
Open to Inactive: Depolarization is also necessary to inactive the channel. Once the channel is open it will then also switch to the inactive state and can not be opened again
Inactive to closed: The channel will not switch back to the closed state until the membrane has repolarized (i.e. gone back towards the original resting membrane potential. Once in the closed state it can then be reopened
Voltage-gated K+ channel (called the delayed rectifying K+ channel)
This channel has only two states, closed and open.
Closed to open: The channel is opened with a strong depolarization, the type you would normally get in an action potential. This channel works to bring the membrane back towards the Nernst potential for K+ i.e. hyperpolarize the membrane
Open to closed: The channel will close when the membrane becomes hyperpolarized or repolarized. Therefore this channel works to shut itself down.
- level of depolarization needed to trigger an action potential (most
neurons have a threshold at -50 mV (i.e. 10 to 15 mV depolarization)
- an action potential is an all or none event, if a nerve is at rest the amplitude on one action potential will be the same all along the nerve independent of the stimulus strength.
- threshold reflects the need to trigger the opening of the voltage-gated sodium channel (need a depolarization of about 10 to 15 mV to open)
- as sodium channels open, Na+ ions flow into cell, depolarizes the cell more and more sodium channels open = a regenerative response - regenerative opening of sodium channels drives the membrane potential towards a peak of the Nernst equilibrium potential for Na+
- during an action potential the membrane potential goes towards the Nernst
equilibrium potential for Na+
- in terms of Goldman-Katz equation now permeability to Na+ is dominant (K+ and Cl- minor components) therefore membrane potential goes towards ENa
- usually falls short of ENa, less driving force on Na+ and the channels begin to inactivate rapidly after activation
- after reaches peak now action potential falls, membrane potential falls
back towards rest
- why? Why doesn't the action potential stay around ENa?
- two reasons:
i) Na+ channels move into an inactive state
ii) delayed K+ channels open (giant axon of squid or non-myelinated axons of vertebrates)
1) Inactivating Na+ channels -
- Na+ channels go to an inactivated state after 1-2 msec after first opening
- inactivated = can NOT be reopened
- therefore the membrane potential now determined mostly by K+ (same as for resting potential) and membrane starts to repolarize
2) Delayed K+ channels open (called delayed rectifier; voltage-gated like Na+ channel)
- open after about 1-2 msec of threshold depolarization
- now K+ flows out of the cell and speeds the repolarization process
- cause the hyperpolarization after the action potential because open K+ channels make the K+ permeability higher than at rest and membrane more negative on inside
-hyperpolarization of membrane causes K+ channels to close
-then membrane settles back to rest
- voltage-gated Na+ channels and voltage-gated K+ channels now closed so
the membrane goes back to the resting state
- i.e. the leak channels are the only channels open and again set the membrane potential
-divided into two parts
i) absolute refractory period
ii) relative refractory period
1) Absolute refractory period
- Na+ channels are inactive and CAN NOT be opened no matter how much the membrane is depolarized at this time
- another action potential can not be generated in this part of the nerve at this time
2) Relative refractory period
- as membrane repolarize's = goes to more negative potentials this triggers the Na+ channels to move from an inactive state to a close state.
- hyperpolarization by the opening of the K+ channels helps this process
- once Na+ channel is in the closed state can be opened again with depolarization
- during relative refractory period, more and more Na+ channels available to be opened and therefore increase the chances of firing an action potential
- If the action potential if all or none how does a nerve convey the
strength of a stimulus?
- e.g. how does a sensory nerve distinguish between a light touch (feather) and a rough abrasive touch (sand paper)?
- the information is indicted by the frequency of the action potentials along the nerve.
-the stimulus strength (current input in to the nerve either experimentally by injecting a large current or in real life by response of touch receptor) triggers different frequency of action potentials
-therefore: light touch - infrequent action potentials; rough touch - more frequent action potentials
- the refractory period limits the frequency of the action potential
- during the relative refractory period an action potential can be generated but with an increased threshold and a reduced amplitude
- increased threshold because have to over come hyperpolarization
- decrease amplitude because less Na+ channels are available to open (many are still in the inactive state) and so get less Na+ flowing into the cell
(in other words the permeability or conductance of Na+ is reduced during relative refractory period - increases towards the end of the period)
- the refractory period also sets the direction of an action potential
- depolarizing current from the action potential can spread passively in either direction
- one way the Na+ channels are in a closed state and are ready to be opened, therefore the spreading current can trigger an action potential in this neighbouring region
- the other way the Na+ channels are in an inactive state and can not be opened therefore the spreading current has no effect on the channels in this region and an action potential is not trigger
Throughout the lectures we will be introducing a wide range of ion channels. These range from leak channels (K+, Na+, Cl- etc.), voltage-gated ion channels (K+, Na+ and Ca+2 etc.) and aligned gated ion channels (K+/Na+, Cl- etc.).
Most of the proteins that make up the different types of ion channels are very similar in their structure and have conserved amino acid sequences. This degree of conservation occurs between different types of channels and across species. So for instance the Drosophila voltage-gated Na+ channel is very similar to the human voltage-gated Na+ channel etc. All the ion channels are composed of alpha helices that span the lipid bilayer. Those that contact the lipid bilayer are composed of hydrophobic amino acids (Phe, Ile, Leu etc.) that span about 20 amino acids. Those alpha helices that line the pore are composed of hydrophilic residues to allow ion flow (Lys, Arg etc.).
All the ion channels in question have a common feature. A pore that allows the ion(s) in question to flow across the lipid bilayer. The pore is specific to a certain ion or ions. For instance the leak K+ channel only allows K+ ions to flow across the membrane.
The voltage sensor is an alpha helix is found in the channel and spans the membrane. The voltage-sensor has positive charges at every third amino acid. The sensor moves in response to depolarization (i.e. the increase positive charge on the interior membrane causes the physical movement of the voltage-sensor). The sensor alpha helix is buried within the channel protein (i.e. protected from hydrophobic lipid bilayer by the rest of the ion channel protein).
The voltage-sensors move in response to depolarization to open the ion
channel. One model of how the voltage-sensor works is based on a twist or
spiral movement that cause the alpha helix to move within the membrane.
Experimenters can measure this movement of the voltage-sensory but you'll have
to wait until Biology 455 to learn all about that.
The following is a movie of one model of how the voltage-sensor moves. (WARNING: a big file!!).
Movie of moving voltage-sensor