Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor

Junichi Nakai, Robert T. Dirksen, Hanh T. Nguyen, Isaac N Pessah, Kurt G. Beam, Paul D. Allen

Research output: Contribution to journalArticle

373 Scopus citations

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 channel and the dihydropyridine receptor (DHPR) functions as the voltage sensor and also as an L-type Ca2+ channel. 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). 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.

Original languageEnglish (US)
Pages (from-to)72-75
Number of pages4
JournalNature
Volume380
Issue number6569
DOIs
StatePublished - Mar 7 1996

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    Nakai, J., Dirksen, R. T., Nguyen, H. T., Pessah, I. N., Beam, K. G., & Allen, P. D. (1996). Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor. Nature, 380(6569), 72-75. https://doi.org/10.1038/380072a0