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 di adic junctional complexes. In cardiac muscle direct physical or functi onal couplings have not been demonstrated. We have tested the hypothes is of functional coupling of L-type Ca2+ channels and ryanodine recept ors in rat cardiac myocytes by comparing the efficacies of Ca2+ in tri ggering Ca2+ release when the ion enters the cell via the Ca2+ channel s or the Na+/Ca2+ exchanger. Ca2+ transported through the Ca2+ channel s was 20-160 times more effective than Ca2+ influx via the Na+/Ca2+ ex changer in gating Ca2+ release from the sarcoplasmic reticulum, sugges ting privileged communication between Ca2+ channels and ryanodine rece ptors. In support of this hypothesis we found that Ca2+ channels were inactivated by Ca2+ release from the sarcoplasmic reticulum, even thou gh the myoplasmic Ca2+ concentrations were buffered with 10 mM EGTA. T he data thus suggest privileged cross signaling between the dihydropyr idine and ryanodine receptors such that Ca2+ flux through either the C a2+ channel or the ryanodine receptor alters the gating kinetics of th e other channel.