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 electrical ly paced, isolated, adult rat myocytes were found to be absolutely dep endent on the presence of a functional SR and were completely abolishe d by the SR Ca2+-ATPase inhibitors cyclopiazonic acid and thapsigargin or by the Ca2+-release channel opener ryanodine. Neonatal rat cardiom yocytes, on the other hand, elicited consistent intracellular Ca2+-tra nsients even after complete functional inhibition of the SR. The trans ients, however, were markedly prolonged. Also isolated adult guinea pi g myocytes maintained the ability to shorten after a complete inhibiti on of the SR Ca2+-ATPase by either thapsigargin or cyclopiazonic acid. The twitches and the intracellular Ca2+-transients, however, were con siderably longer after inhibition of the SR Ca2+-ATPase. Different res ults were obtained after preincubation of the cells with 10 mu M ryano dine 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 Ca2+-pump inhibitor was added to ryanodine-treat ed cells, the size of the Ca2+-transients and the capacity of the cell s to shorten increased. Ryanodine leaves the activity of the Ca2+-pump of the SR intact and thus leads to an underestimation of the amount o f excitatory Ca2+ flowing into the cell. The results show that, while the significance of the SR in regulating the Ca2+-transients and short ening of cardiomyocytes varies depending on the species and the stage of development, SR function is of paramount importance for the occurre nce of rapid twitches.