Functional Implications of Calcium Channel Modulation in Embryonic Dorsal Root Ganglion Neurons

Abstract

The calcium-dependence of neurosecretion was established more than two decades ago (1). Electrophysiological demonstration of voltage-dependent calcium (Ca) channels in the presynaptic terminal of the squid giant synapse (2) led to the notion that Ca influx through these channels provided the necessary trigger for transmitter release. The relatively recent demonstrations of multiple Ca channel types (3–7) has prompted speculation as to their functional significance; for example, is one type of Ca channel important for regulating threshold and another for controlling exocytosis? If so, these functional differences imply spatial segregation of the various channel subtypes—e.g., those important for secretion would necessarily be located at sites of transmitter release. To address this question, we have begun to investigate the Ca-dependent release of substance P from dorsal root ganglion (DRG) neurons and its control by transmitter receptors and GTP-binding proteins. The results of experiments summarized in this chapter argue that L-type Ca channels (as defined by Tsien and collaborators, see below) play a critical role in exocytosis (8) and their regulation by neurotransmitters and GTP-binding proteins (9) has important functional implications for neurotransmission.