CaV1.1: The atypical prototypical voltage-gated Ca2+ channel.

Abstract: CaV1.1 is the prototype for the other nine known CaV channel isoforms, yet it has functional properties that make it truly atypical of this group. Specifically, CaV1.1 is expressed solely in skeletal muscle where it serves multiple purposes; it is the voltage sensor for excitation–contraction coupling and it is an L-type Ca2+ channel which contributes to a form of activity-dependent Ca2+ entry that has been termed Excitation-coupled Ca2+ entry. The ability of CaV1.1 to serve as voltage-sensor for excitation–contraction coupling appears to be unique among CaV channels, whereas the physiological role of its more conventional function as a Ca2+ channel has been a matter of uncertainty for nearly 50years. In this chapter, we discuss how CaV1.1 supports excitation–contraction coupling, the possible relevance of Ca2+ entry through CaV1.1 and how alterations of CaV1.1 function can have pathophysiological consequences. This article is part of a Special Issue entitled: Calcium channels. [Copyright &y& Elsevier]