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Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor

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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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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