Ca(V)1.1: The atypical prototypical voltage-gated Ca²⁺ channel.

Ca(V)1.1 is the prototype for the other nine known Ca(V) channel isoforms, yet it has functional properties that make it truly atypical of this group. Specifically, Ca(V)1.1 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 Ca(V)1.1 to serve as voltage-sensor for excitation-contraction coupling appears to be unique among Ca(V) channels, whereas the physiological role of its more conventional function as a Ca²⁺ channel has been a matter of uncertainty for nearly 50 years. In this chapter, we discuss how Ca(V)1.1 supports excitation-contraction coupling, the possible relevance of Ca²⁺ entry through Ca(V)1.1 and how alterations of Ca(V)1.1 function can have pathophysiological consequences. This article is part of a Special Issue entitled: Calcium channels.