Functional coupling of Ca2+ channels and ryanodine receptors in cardiac myocytes.
In skeletal muscle, dihydropyridine receptors are functionally coupled to ryanodine receptors of the sarcoplasmic reticulum in triadic or diadic junctional complexes. In cardiac muscle direct physical or functional couplings have not been demonstrated. We have tested the hypothesis of functional coupling of L-type Ca2+ channels and ryanodine receptors in rat cardiac myocytes by comparing the efficacies of Ca2+ in triggering Ca2+ release when the ion enters the cell via the Ca2+ channels or the Na+/Ca2+ exchanger. Ca2+ transported through the Ca2+ channels was 20-160 times more effective than Ca2+ influx via the Na+/Ca2+ exchanger in gating Ca2+ release from the sarcoplasmic reticulum, suggesting privileged communication between Ca2+ channels and ryanodine receptors. In support of this hypothesis we found that Ca2+ channels were inactivated by Ca2+ release from the sarcoplasmic reticulum, even though the myoplasmic Ca2+ concentrations were buffered with 10 mM EGTA. The data thus suggest privileged cross signaling between the dihydropyridine and ryanodine receptors such that Ca2+ flux through either the Ca2+ channel or the ryanodine receptor alters the gating kinetics of the other channel.
Sham
J S
JS
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University Medical School, Baltimore, MD 21205.
Cleemann
L
L
Morad
M
M
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009124:Muscle Proteins / Q000502:physiology*; D009532:Nickel / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; D013779:Tetrodotoxin / Q000494:pharmacology
D015220:Calcium Channels; D002352:Carrier Proteins; D005456:Fluorescent Dyes; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; D012433:Ryanodine; D001464:Barium; D002110:Caffeine; D013779:Tetrodotoxin; D004533:Egtazic Acid; D009532:Nickel; D002118:Calcium