The molecular transition that confers voltage dependence to muscle contraction

Marina Angelini (), Nicoletta Savalli, Federica Steccanella, Savana Maxfield, Serena Pozzi, Marino DiFranco, Stephen C. Cannon, Antonios Pantazis and Riccardo Olcese ()
Additional contact information
Marina Angelini: University of California Los Angeles
Nicoletta Savalli: University of California Los Angeles
Federica Steccanella: University of California Los Angeles
Savana Maxfield: University of California Los Angeles
Serena Pozzi: Linköping University
Marino DiFranco: University of California Los Angeles
Stephen C. Cannon: University of California Los Angeles
Antonios Pantazis: Linköping University
Riccardo Olcese: University of California Los Angeles

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract What is the molecular origin of voltage dependence in skeletal muscle excitation-contraction? Cholinergic transmission to the muscle fiber triggers action potentials, which are sensed by voltage-gated L-type calcium channels (CaV1.1). In turn, the conformational changes in CaV1.1 propagate to and activate intracellular ryanodine receptors (RyR1), causing Ca2+ release and contraction. The CaV1.1 channel has four voltage-sensing domains (VSD-I to -IV) with diverse voltage-sensing properties, so the identity of VSD(s) responsible for conferring voltage dependence to RyR1 opening, is unknown. Using voltage-clamp fluorometry, we show that only VSD-III possesses kinetic, voltage-dependent and pharmacological properties consistent with skeletal-muscle excitability and Ca2+ release. We propose that the earliest voltage-dependent event in the excitation-contraction process is the structural rearrangement of VSD-III that propagates to RyR1 to initiate Ca2+ release and contraction.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-59649-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59649-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-59649-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().