Receptor-mediated regulation of calcium channels and neurotransmitter release

Ca²⁺ influx into the nerve terminal is normally the trigger for the release of neurotransmitters. Many neurons possess presynaptic receptors whose activation results in changes in the quantity of neurotransmitter released by an action potential. This paper reviews studies that show that presynaptic receptors can regulate the activity of Ca²⁺ channels in the nerve terminal, resulting in changes in the influx of Ca²⁺ and in neurotransmitter release. Neurons possess several different types of voltage-sensitive Ca²⁺ channels. Ca²⁺ influx through N-type channels appears to trigger transmitter release in many instances. In other cases Ca²⁺ influx through L channels can influence transmitter release. Neurotransmitters can inhibit N channels through a G protein-mediated transduction mechanism. The G proteins are frequently pertussis toxin substrates. Inhibition of N channels appears to involve changes in their voltage dependence. Neurotransmitters can also regulate neuronal K⁺ channels. Activation of these K⁺ channels can lead to a reduction in Ca²⁺ influx and neurotransmitter release; these effects are also mediated by G proteins. Thus neurotransmitters may often regulate both presynaptic Ca²⁺ and K⁺ channels. These two effects may be synergistic mechanisms for the regulation of Ca²⁺ influx and neurotransmitter release.