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Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor

Nature volume 380, pages 72–75 (1996)Cite this article

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

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  1. Junichi Nakai
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  2. Robert T. Dirksen
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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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