NERVE CELLS : THE ACTION POTENTIAL : Ionic Movements
During the action potential there are rapid transient changes in the transmembrane potential: at its peak the membrane potential reaches nearly +40 mV (approaching the equilibrium potential for sodium), then rapidly declines to below the previously existing resting potential (a phase known as the afterpotential) before slowly returning to normal.
Action potentials are initiated by depolarisation of the resting membrane to a threshold membrane potential of about -55 mV, at which point voltage-gated sodium channels open and allow sodium ions to enter the axoplasm.
The repolarisation phase of the action potential is due to the inactivation and closure of voltage gated sodium channels and the opening of voltage-gated potassium channels, which are also responsible for the afterpotential.
The voltage-gated sodium channel behaves as though it has two gates:
the first opens on depolarisation to around -55mV
the second stops inward movement of sodium ions by closing the channel at a different site within the protein pore as soon as the depolarisation has occurred - the latter is know as the inactivation gate.
During the depolarisation phase of the action potential (the 'spike'), some sodium ions enter the axon when the voltage-gated sodium channel opens and cease when the gate is inactivated. During this period the axon in inexcitable (during the absolute refractory period)
Once the depolararisation phase has occurred, voltage gated sodium channels become inactivated and voltage gated potassium channels begin to open.
The opening and closure of voltage-gated potassium channels following the spike are essential for repolarisation (and for the afterpotential, during which the axon is less excitable than normal (the relative refractory period).
Voltage gated sodium channels (also called Nav channels) are composed of proteins that change their shape to allow sodium ions to move when the voltage gate opens and before the inactivation gate closes. Mutations of these proteins allow different rates of sodium entry, and for different periods.
One mutation is associated with certain chronic pain states, because the action potential is prolonged, resulting in increased transmitter release at synapses the pain pathway.
Key Words: Action potential, 'Spike', voltage gated sodium channels, the inactivation gate; voltage gated potassium channels, Nav channels.
How are voltage changes generated during the Action Potential
The diagram shows the opening and closing of membrane channels during the action potential.
Ionic Basis of the Action Potential
Whenever depolarization of the axon reaches threshold (i.e., when the resting potential is around - 50 to -55 mv), voltage-sensitive sodium channels in the membrane open. As a consequence some Na+ ions move into the cell down both electrical and concentration gradients towards the Na+ equilibrium potential (about +60 mV) and cause the membrane potential to reverse for less than a millisecond.
Action potentials are generated when voltage-gated sodium channels open as a result of the passage of local electrical currents across the membrane.
The repolarisation phase of the action potential is due to the opening of voltage-gated potassium channels, which cause the membrane potential to move rapidly towards the equiibrium potential of potassium.
The 'spike' of the action potential lasts around 1 millisecond.
Currents carried by different ions during the Action Potential
The diagram shows the sodium and potassium currents during the action potential and the changes in excitability of the axon.
Ionic Currents during the Action Potential
The top panel of the diagram shows the states of voltage-gated sodium and potassium channels during the action potential. Note that the voltage-gated sodium channel has a voltage-sensitive gate and an inactivation gate (more details below).
A technique called voltage clamping is used to measure the time course of ionic movements across the cell membrane.
The diagram shows the time course of sodium and potassium currents. The sodium current peaks rapidly and decays as the inactivation gate closes.
Potassium currents peak later and are more prolonged and continue throughout the afterpotential.
The bottom section of the diagram shows thechanges in excitability f the axon to electrical stimulation. The excitability is zero during the absolute refractory period - when sodium channels are open or inactivated. The excitability returns to normal during the relative refractory period - i.e. during the afterpotential.
Image source : Wikispaces
Model of a Voltage-gated channel. The bottom diagram shows the closed voltage-gated sodium channel at the normal resting potential. Depolarisation opens the voltage-gated channel allowing sodium entry (top left) Once depolarised the inactivation gate, shown by the ball and chain, closes, limiting the number of sodium ions that move across the membrane (top right).
Molecular Biology of Voltage-gated Sodium Channels
There are several types of voltage-gated sodium channels in electrically excitable tissues, called Nav channels (with subtypes 1.1 thru 1.9). These structurally distinct isoforms give rise to the voltage gated sodium channels in muscle and cardiac muscle (Nav1.4 and 1.5) as well as in nerve. In the brain there is a subfamily of isoforms (Nav1.1, 1.2 and 1.3)
Nav1.7 is expressed particularly in the small dorsal root ganglion (sensory) neurones and in the autonomic ganglia.
In certain neurological disorders, isoforms that are not normally expressed can appear in neurones. An example is given below and concerns the expression of unusual isoforms in damaged neurones, and in inflammation.
Nav1.8 and 1.9 inactivate more slowly than Nav1.7, and this difference is likely to affect the generation and propagation of action potentials, and alter transmitter release at nerve terminals.
Nav1.8 is known to be involved in hyperalgesia and allodynia in experimental investigations; studies of Nav1.8 knockout mice have shown that the channel is associated with inflammatory and neuropathic pain.
Nav1.8 is expressed in damaged sensory axons and is thought to be responsible for the spontaneous generation of cation potentials in nociceptive afferents.
The presence of Nav1.9 is associated with hypersensitivity to heat and mechanical stimuli in inflammatory pain.