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 Ca²⁺-ATPase inhibitors cyclopiazonic acid and thapsigargin or by the Ca²⁺-release channel opener ryanodine.Neonatal rat cardiomyocytes, on the other hand, elicited consistent intracellular Ca²⁺-transients even after complete functional inhibition of the SR. The transients, however, were markedly prolonged. Also isolatedadult guinea pig myocytes maintained the ability to shorten after a complete inhibition of the SR Ca²⁺-ATPase by either thapsigargin or cyclopiazonic acid. The twitches and the intracellular Ca²⁺-transients, however, were considerably longer after inhibition of the SR Ca²⁺-ATPase. Different results were obtained after preincubation of the cells with 10 M 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 Ca²⁺-pump inhibitor was added to ryanodine-treated cells, the size of the Ca²⁺-transients and the capacity of the cells to shorten increased. Ryanodine leaves the activity of the Ca²⁺-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 Ca²⁺-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.Abbreviations EGTA ethylene glycol-bis-(beta amino ethyl ether)N,N,N,N tetraacetic acid - MOPS morpholinopropane sulfonic acid - SR sarcoplasmic reticulum - BSA bovine serum albumin - HEPES N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid