The role of the sarcoplasmic reticulum in various types of cardiomyocytes.
The relative importance of the sarcoplasmic reticulum (SR) as a source of Ca2+ in the excitation-contraction coupling of mammalian myocytes was tested. Shortening and intracellular Ca2+ transients of electrically paced, isolated, adult rat myocytes were found to be absolutely dependent on the presence of a functional SR and were completely abolished by the SR Ca(2+)-ATPase inhibitors cyclopiazonic acid and thapsigargin or by the Ca(2+)-release channel opener ryanodine. Neonatal rat cardiomyocytes, on the other hand, elicited consistent intracellular Ca(2+)-transients even after complete functional inhibition of the SR. The transients, however, were markedly prolonged. Also isolated adult guinea pig myocytes maintained the ability to shorten after a complete inhibition of the SR Ca(2+)-ATPase by either thapsigargin or cyclopiazonic acid. The twitches and the intracellular Ca(2+)-transients, however, were considerably longer after inhibition of the SR Ca(2+)-ATPase. Different results were obtained after preincubation of the cells with 10 microM ryanodine to induce emptying of the SR Ca2+ pool. In this case, Ca2+ spikes and twitches were also markedly reduced in size, in addition to being prolonged. When a SR Ca(2+)-pump inhibitor was added to ryanodine-treated cells, the size of the Ca(2+)-transients and the capacity of the cells to shorten increased. Ryanodine leaves the activity of the Ca(2+)-pump of the SR intact and thus leads to an underestimation of the amount of excitatory Ca2+ flowing into the cell. The results show that, while the significance of the SR in regulating the Ca(2+)-transients and shortening of cardiomyocytes varies depending on the species and the stage of development, SR function is of paramount importance for the occurrence of rapid twitches.
Pharmaceuticals Division, Ciba-Geigy Ltd., Basel, Switzerland.
M
M
Chiesi
A
A
Wrzosek
S
S
Grueninger
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000254:growth & development; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*
D012433:Ryanodine; D002118:Calcium