Nifedipine binding to human Cav1.1 allosterically sets 3 out of 4 voltage sensors into their “relaxed state”

Marina Angelini,Nicoletta Savalli,Federica Steccanella,Riccardo Olcese

doi:10.1016/j.bpj.2021.11.2223

Marina Angelini, Nicoletta Savalli + Show 2 more

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https://doi.org/10.1016/j.bpj.2021.11.2223

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Journal: Biophysical Journal	Publication Date: Feb 1, 2022
License type: publisher-specific-oa

Affiliation: University of California, Los Angeles

Abstract

The excitation-contraction (E-C) of skeletal muscles is initiated by the voltage-dependent rearrangements of the L-type Ca2+ channel (CaV1.1). CaV1.1 possesses four heterologous Voltage-Sensing Domains (VSDs) that control both its pore and RYR1 (Savalli, JGP 2021). Paradoxically, while Ca2+ influx through the CaV1.1 is not necessary for skeletal muscle E-C coupling, the CaV channel blocker nifedipine has been shown to alter contraction in different species. We recently provided evidence that nifedipine modifies the CaV1.1 voltage-sensing apparatus (Angelini, Biophys.

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