Enhanced dihydropyridine receptor channel activity in the presence of ryanodine receptor.
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.
Nakai
J
J
Department of Medical Chemistry, Kyoto University Faculty of Medicine, Japan.
Dirksen
R T
RT
Nguyen
H T
HT
Pessah
I N
IN
Beam
K G
KG
Allen
P D
PD
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D018390:Gene Targeting; D008564:Membrane Potentials; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D012433:Ryanodine / Q000378:metabolism* / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel; D015398:Signal Transduction
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D018076:DNA, Complementary; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002110:Caffeine; D002118:Calcium