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Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor

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Abstract

EXCITATION-CONTRACTION coupling in skeletal muscle involves a voltage sensor in the plasma membrane which, in response to depolarization, causes an intracellular calcium-release channel to open. The skeletal isoform of the ryanodine receptor (RyR-1) functions as the Ca2+-release channel1–3 and the dihydropyridine receptor (DHPR) functions as the voltage sensor and also as an L-type Ca2+ channel4,5. Here we examine the possibility that there is a retrograde signal from RyR-1 to the DHPR, using myotubes from mice homozygous for a disrupted RyR-1 gene (dyspedic mice)3. As expected, we find that there is no excitation–contraction coupling in dyspedic myotubes, but we also find that they have a roughly 30-fold reduction in L-type Ca2+-current density. Injection of dyspedic myotubes with RyR-1 complementary DNA restores excitation–contraction coupling and causes the density of L-type Ca2+ current to rise towards normal. Despite the differences in Ca2+-current magnitude, measurements of charge movement indicate that the density of DHPRs is similar in dyspedic and RyR-1-expressing myotubes. Our results support the possibility of a retrograde signal by which RyR-1 enhances the function of DHPRs as Ca2+ channels.

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Author notes

  1. Junichi Nakai

    Present address: Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, Colorado, 80523, USA

  2. Paul D. Allen: To whom correspondence should be addressed.

Authors and Affiliations

  1. Department of Medical Chemistry, Kyoto University Faculty of Medicine, Kyoto, 606-01, Japan

    Junichi Nakai

  2. Department of Anatomy and Neurobiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, 80523, USA

    Junichi Nakai, Robert T. Dirksen & Kurt G. Beam

  3. Department of Cardiology, Laboratory of Molecular Cardiology, Children's Hospital, Boston, Massachusetts, 02115, USA

    Hanh T. Nguyen & Paul D. Allen

  4. Department of Molecular Biosciences, University of California-Davis, School of Veterinary Medicine, Davis, California, 95616, USA

    Isaac N. Pessah

  5. Department of Anesthesiology, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts, 02115, USA

    Paul D. Allen

Authors
  1. Junichi Nakai
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  2. Robert T. Dirksen
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  3. Hanh T. Nguyen
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  4. Isaac N. Pessah
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  5. Kurt G. Beam
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Nakai, J., Dirksen, R., Nguyen, H. et al. Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor. Nature 380, 72–75 (1996). https://doi.org/10.1038/380072a0

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  • DOI: https://doi.org/10.1038/380072a0

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