Voltage-gated calcium channels play a critical role in the regulation of cellular function in all excitable cell. First, CA2+ entry through the channel is crucial to the tranduction of electrical signals into specific cellular responses including neurotransmitter release and hormone secretion, regulation of excitability via Ca-activated ionic channels, contraction, regulation of gene transcription, etc. Second, because of their voltage-dependent properties, the channels are important elements contributing to the excitable properties of cells. Recent electrophysiological and pharmacological experiments have demonstrated that voltage-gated calcium channels constitute a family of diverse, but related, proteins. Three types of calcium channels have been characterized in dorsal root ganglion (DRG) cells and have been termed L-, N-, and T-types. The channel types vary in their time-and voltage-dependent properties, and pharmacological properties. They may also be responsible for different functional responses. One of the fundamental questions in neuroscience concerns the regulation of transmitter and neuromodulator release. The role of the different types of calcium channels in secretory processes will be assessed in this proposal by: l) utilizing patch clamp recording techniques to characterize the types of calcium channels present in a preparation of nerve terminals and in an endocrine cell line; 2) studying the modulation of calcium channel activity by transmitters/neuromodulators and their associated second messenger systems in these preparations; 3) monitoring hormone release with radioimmunoassay techniques while manipulating calcium channel activity. All signalling in the nervous system consists of electrical impulses which are translated into chemical messages at neuronal synapses. Since channels underlie this transduction of electrical to chemical signals, information about their properties is critical to understanding all aspects of normal and abnormal nervous system function.
