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.
Miller
R J
RJ
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology
D015220:Calcium Channels; D018377:Neurotransmitter Agents; D015221:Potassium Channels; D017981:Receptors, Neurotransmitter; D019204:GTP-Binding Proteins