Molecular diversity of Ca2+ channel beta subunits.

Introduction Voltage-gated Ca2+ channels have been extensively characterized in terms of their pharmacological, electrophysiological, biochemical, and molecular biological properties. Calcium channels are multisubunit complexes composed of an ion-conducting subunit, a ,, and smaller accessory subunits. Molecular cloning studies have concentrated on the a , subunit because it appears to determine the pharmacological and electrophysiological properties of the channel. In fact, expression of cloned a, subunits from skeletal muscle and cardiac muscle displayed I>-type CaZc-channel activity, whereas other distinct, yet related, a I subunits display N-type activity [l-31. So far, cDNAs from six a , genes have been cloned. Alignment of the deduced amino acid sequences reveals that these a,s are members of a superfamily that can be subdivided into I,-type and non-L-type Ca2+ channels. Despite experiments showing that the accessory subunits are capable of modulating the properties of a , subunits [2,4], cloning of these subunits has until recently received little attention. In this report, we summarize our cloning of Psubunit cDNAs derived from four distinct genes and present new data on alternatively spliced forms. We also summarize our expression studies using a representative member of each of these P subclasses.