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The molecular transition that confers voltage dependence to muscle contraction

Author

Listed:
  • 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
    Linköping University)

  • Riccardo Olcese

    (University of California Los Angeles
    University of California Los Angeles)

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.

Suggested Citation

  • Marina Angelini & Nicoletta Savalli & Federica Steccanella & Savana Maxfield & Serena Pozzi & Marino DiFranco & Stephen C. Cannon & Antonios Pantazis & Riccardo Olcese, 2025. "The molecular transition that confers voltage dependence to muscle contraction," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59649-7
    DOI: 10.1038/s41467-025-59649-7
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