Advances in Ca_V1.1 gating: New insights into permeation and voltage-sensing mechanisms

ABSTRACT

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.

KEYWORDS:

• Skeletal muscle
• Ca_V1.1
• dihydropyridine receptor (DHPR)
• calcium channel
• voltage-sensor
• excitation-contraction (EC) coupling
• voltage-clamp
• functional site-directed fluorometry

Data sharing statement

All journal articles cited in this work are listed on PubMed (https://pubmed.ncbi.nlm.nih.gov), except for reference 44, which can be found on the publisher’s website.

Acknowledgments

We thank Professor Dr. Martin F. Schneider for his steadfast support and insightful comments on the manuscript, and Dr. Filip Van Petegem for helpful discussions. We apologize to those colleagues whose contributions were not mentioned in this review.

Disclosure statement

No potential conflict of interest was reported by the author(s). This work was prepared while R.A.B. was employed at the University of Maryland Baltimore. Dr. Bannister’s current address: National Institutes of Health, Center for Scientific Review, Division of Neuroscience, Development and Aging, 6701 Rockledge Drive MSC 7768, Bethesda, MD, USA 20892. The opinions expressed in this article are the authors’ own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services or the United States government.

Author contributions

All the authors wrote the paper and approved the final manuscript.

Additional information

Funding

This work was supported by the National Institutes of Health grants R01-AR075726 and R01-NS103777 and training grant T32-AR007592.