Voltage gated ion channels
As already mentioned ion channels are pores in the membrane of a cell which allow ions to pass through the otherwise impermeable membrane. These channels can be gated (i.e. opened) by various things. In this chapter we will look at ion channels which can be gated by the voltage across the cells membrane itself, or voltage-gated ion channels.
There are many individual kinds of voltage-gated ion channels, but all we will be concerned about are three large families, voltage-gated sodium, potassium and calcium ion channels; channels, which when open pass sodium, potassium and calcium respectively.
The most important function of two of these voltage gated ion channels is to generate the action potential. The action potential is a often thought of as an electrical signal which passes down the axons of neurons, like current down a wire. In reality it is caused by a chain reaction of voltage gated ion channels opening. The third channel is responsible for converting the electrical nature of the action potential into chemical signals a neuron can deal with.
If a part of a neuron expressing voltage gated sodium and potassium channels (usually the axon and cell body) became depolarized (less positive) to around –50mV, voltage gated ion channels start to become active i.e. they reach threshold. At the cell body, the fastest activating voltage gated ion channel is the sodium channel. The sodium channels start to open, allowing Na+ to enter the cell, further depolarizing the cell, encouraging more sodium channels to open. The Na+ passively diffuses down the axon of the neuron, causing neighboring areas of neurons to become depolarized, where further voltage gated sodium channels open. This causes a chain reaction of Na+ entering the cell, depolarizing close-by areas of cell, opening further sodium channels, causing more Na+ to pour into the cell etc… If this were to happen unabated, the neuron would fire one action potential, Na+ would reach its equilibrium potential and the cell would become electrically dead. But two things happen to stop this, 1) sodium channels inactivate and 2) slower activating potassium channels being to open.
Inactivation of sodium channels happens normally around 1 millisecond after they begin to open. Inactivation is a transient block of a channel, which in the case of voltage gated sodium channels is caused by a length of the protein which forms the channel, physically blocking the channel like a cork. This inactivation limits both the time and voltage of the action potential. As stated, inactivation is transient, and if the neuron wasn’t returned to its resting potential, or at least below threshold, as soon as inactivation passed, the sodium channels would open again. This is when voltage gated potassium channels began to play their part. As potassium channels take about 1-2ms to open after they reach threshold, they are beginning to become fully activated when sodium channel inactivation is in full swing. K+ ions being to flood out of the cell, rapidly making the neuron more negative (repolarizing). Potassium channels do not show inactivation, but as they act to repolarize the cell the pull it below the threshold for sodium and potassium channel activation, which closes the potassium channels.
Importantly the action potential is all-or-none, that is to say, the body can’t code information in the amplitude of the action potential, the action potential either happens or it doesn’t. The body codes information in the frequency of action potentials. For instance, in neurons which transmit pain, more painful stimuli causes the neurons to fire more frequently, but with the same amplitude. Cocaine, apart from its well-known action of increasing dopamine, also blocks voltage gated sodium channels, which stops the formation and propagation of the action potential. This is why it causes numbness, by blocking the transmission in sensory neurons.
Finally, when the action potential has travelled the whole length of the axon, it depolarizes the ends of the neuron, (usually -synaptic terminals-), here voltage gated calcium channels can open, causing Ca2+ to enter the cell. This Ca2+ influx causes neurotransmitter release (as described in the synapse). Although this Ca2+ influx shares many properties with the sodium/potassium action potential, it is not all-or-none. Alcohol is believed to inhibit Ca2+ channel function directly (Hendricson et al., 2003), and many common drugs effects Ca2+ channel indirectly. For instance, D9-THC from cannabis and yohimbine from Yohimbe. By effecting Ca2+ influx, these drugs effect neurotransmitter release (discussed further in the synapse and G-Protein Coupled Receptors, and signalling cascades).
References
Hendricson AW, Thomas MP, Lippmann MJ, Morrisett RA. Suppression of L-type voltage-gated calcium channel-dependent synaptic plasticity by ethanol: analysis of miniature synaptic currents and dendritic calcium transients. J Pharmacol Exp Ther. 2003;307(2):550-8