Contributions of two classes of calcium channels to transmitter release and plasticity in the sensory neurons of Aplysia.

摘要

The finding of several types of voltage-gated calcium channels in neurons has prompted an analysis of the roles of different channel types in the cellular processes that are directly regulated by calcium influx. The most widely studied of these processes is the secretion of neurotransmitter substances. Using Aplysia sensory and motor neurons in cell culture, it has been possible to examine the roles of two components of calcium current in the physiological release of neurotransmitter from the synaptic terminals of sensory neurons, and to determine their relative roles in four forms of synaptic plasticity.; The calcium current was found to consist of two components with distinct kinetics and pharmacology: a slowly inactivating, dihydropyridine-sensitive current that is similar to the L-type calcium current found in vertebrate neurons, and a rapidly inactivating, dihydropyridine-insensitive current that resembles the vertebrate neuronal N-type calcium current.; Although calcium influx is required for transmitter release from sensory neurons, pharmacological blockade of the slowly inactivating current has no significant effect on release. Furthermore, the slowly inactivating current also does not appear to contribute to three forms of synaptic plasticity in sensory neurons: presynaptic inhibition, homosynaptic depression and heterosynaptic facilitation. This current does contribute, however, to a fourth form of plasticity that is manifest as a modulation of transmitter release induced by tonic depolarization of the sensory neuron.; The finding that the slowly inactivating current is not required for most forms of plasticity is particularly interesting in the case of heterosynaptic facilitation. Facilitatory transmitters such as serotonin enhance release in part by increasing calcium influx during an action potential. Previous experiments (Klein and Kandel, 1980) indicated that increased influx was mediated indirectly, resulting from broadening of the action potential due to down modulation of K{dollar}sp+{dollar} current. It is now apparent that serotonin also increases calcium influx directly by enhancing the slowly inactivating calcium current. Modulation of this slowly inactivating current does not, however, appear to contribute to the facilitation of release. The calcium influx required for release and for the expression of several forms of plasticity appears to be contributed by the rapidly inactivating calcium channels.