Functional interconversion of rest decay and ryanodine effects in rabbit and rat ventricle depends on Na/Ca exchange.
Rapid cooling contractures were used to assess changes in sarcoplasmic reticulum (SR) Ca content in isolated rabbit and rat ventricular muscle during rest, with altered transsarcolemmal [Na] and [Ca] gradients and in the presence and absence of 100 nM ryanodine. In rabbit there is normally a rest-duration dependent decline in SR Ca content (rest decay), whereas in rat there is a short-term increase in SR Ca content (rest potentiation) and little evidence of rest decay. Ryanodine greatly accelerates the rate of rest decay in rabbit, depleting the SR of Ca in approximately 1 s, whereas in rat, ryanodine does not appear to drain the SR even after a 10 min rest. Elevation of intracellular Na activity in rabbit (by Na-pump inhibition) to a level similar to that measured in control rat during rest (Shattock and Bers, Am. F. Physiol., 256: C813-C822, 1989) makes rest-dependent changes of SR Ca content in these two tissues similar. The rest decay in rabbit in the presence of ryanodine is also markedly slowed after Na-pump inhibition. In rat, reduction of [Ca]0 allows rest decay to occur (+/- ryanodine), but this rest decay can be largely prevented by simultaneous reduction of [Na]o (to maintain [Na]3/[ Ca] constant) which serves to keep the thermodynamic driving force on a 3:1 Na/Ca exchange constant. We conclude that the process of rest decay and rest potentiation in both rabbit and rat ventricle depends on the sarcolemmal Na/Ca exchange. Furthermore, these species can be functionally interconverted by manipulation of the [Na] and [Ca] gradients. The ability of ryanodine to deplete the SR of Ca also depends critically on other transport systems (particularly Na/Ca exchange) to remove Ca from the cytoplasm.
Bers
D M
DM
Division of Biomedical Sciences, University of California, Riverside 92521-0121.
Christensen
D M
DM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology; D011817:Rabbits; D051381:Rats; D012146:Rest / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D016276:Ventricular Function
D012433:Ryanodine; D012964:Sodium; D002118:Calcium