The function of C2+ channel subtypes in exocytotic secretion:: new perspectives from synaptic and non-synaptic release

By mediating the Ca2+ influx that triggers exocytotic fusion, Ca2+ channels play a central role in a wide range of secretory processes. Ca2+ channels consist of a complex of protein subunits, including anal subunit that constitutes the voltage-dependent Ca2+-selective membrane pore, and a group of auxiliary subunits, including beta, gamma, and alpha(2)-delta subunits, which modulate channel properties such as inactivation and channel targeting. Subtypes of Ca2+ channels are constituted by different combinations of alpha(1) subunits (of which 10 have been identified) and auxiliary subunits, particularly beta (of which 4 have been identified). Activity-secretion coupling is determined not only by the biophysical properties of the channels involved, but also by the relationship between channels and the exocytotic apparatus, which may differ between fast and slow types of secretion. Colocalization of Ca2+ channels at sites of fast release may depend on biochemical interactions between channels and exocytotic proteins. The aim of this article is to review recent work on Ca2+ channel structure and function in exocytotic secretion. We discuss Ca2+ channel involvement in selected types of secretion, including central neurotransmission, endocrine and neuroendocrine secretion, and transmission at graded potential synapses. Several different Ca2+ channel subtypes are involved in these types of secretion, and their function is likely to involve a variety of relationships with the exocytotic apparatus. Elucidating the relationship between Ca2+ channel structure and function is central to our understanding of the fundamental process of exocytotic secretion. (C) 2002 Elsevier Science Ltd. All rights reserved.