Advances in CaV1.1 gating: New insights into permeation and voltage-sensing mechanisms.

The Ca_V1.1 voltage-gated Ca²⁺ channel carries L-type Ca²⁺ current and is the voltage-sensor for excitation-contraction (EC) coupling in skeletal muscle. Significant breakthroughs in the EC coupling field have often been close on the heels of technological advancement. In particular, Ca_V1.1 was the first voltage-gated Ca²⁺ channel to be cloned, the first ion channel to have its gating current measured and the first ion channel to have an effectively null animal model. Though these innovations have provided invaluable information regarding how Ca_V1.1 detects changes in membrane potential and transmits intra- and inter-molecular signals which cause opening of the channel pore and support Ca²⁺ release from the sarcoplasmic reticulum remain elusive. Here, we review current perspectives on this topic including the recent application of functional site-directed fluorometry.