N-type Ca2+ channel.

Abstract

Ca(2+) entry through voltage-dependent Ca(2+) channels (VDCCs) regulates various aspects of physiological function, including neurotransmitter release, regulation of cell membrane excitability, and control of gene expression. VDCCs are classified into several sub-types (L-, N-, P/Q-, R-, and T-types) based on electrophysiological and pharmacological properties. Each type of channels except the T-type is composed of at least four subunits, designated alpha(1), alpha(2), beta, and delta. During the past decade, a number of genes encoding these subunits have been cloned, and cDNA expression studies using heterologous expression systems have revealed the intricate nature of subunit interaction and many biophysical aspects of channel function. In recent years, an entirely new strategy has been introduced in attempts to clarify the physiological role of each of the VDCCs, and this has proven to be very useful in defining previously unknown in vivo functions of VDCCs. In this article, we briefly review the recent advances in our understanding of VDCCs with special emphasis on the N-type channel, which is mainly expressed in neural tissues and is the essential component of neurotransmitter release. We will mainly discuss the subunit composition, channel regulation by G proteins and exocytotic proteins, and the mouse phenotypes in which N-type channel subunits have been deleted by gene targeting technology.