Voltage-gated calcium channels

Abstract

Publisher Summary Voltage-gated calcium channels have been extensively investigated by conventional electrophysiological and biochemical techniques. However, the advances of cloning and functional expression techniques have opened a new, broader view of these macromolecular structures. This chapter discusses the information obtained using conventional techniques. It focuses on recent studies addressing the molecular and functional diversity of voltage-gated calcium channels (VGCCs) that have provided an insight into the functional subunit structure of these channels. Excitable cells can contain multiple types of VGCCs. Different criteria are used to classify these channels. When defined by the pattern of channel activation, two major classes appear low voltage-activated (LVA) and high voltage-activated (HVA) channels. LVA channels have been termed as T-type (T stands for transient or tiny), while HVA channels have been further divided into four subclasses: L-type (L stands for long-lasting), N-type (“N” stands for neither “L” nor “T,” or more recently, neuronal), P-type (first described in cerebellar Purkinje cells), and a fifth channel type that cannot be placed into any of these subclasses. Voltage-gated Ca2+ channels are multi-subunit protein complexes that form a highly selective ion pore in the membrane. The α1-subunit forms the channel pore, voltage sensor, and harbors the clinically important drug-binding sites. Molecular technology is beginning to elucidate roles for the other subunits. These channels represent an important group of macromolecular structures that contribute to the regulation of intracellular Ca2+ concentration, a critical factor in numerous cellular processes.