A POSSIBLE MECHANISM FOR LARGE STRETCH-INDUCED INCREASE IN [CA2-PIG VENTRICULAR MYOCYTES(](I) IN ISOLATED GUINEA)

Objectives: The aim of the study was to investigate the mechanisms res ponsible for provoking and maintaining a large, ig stretch-induced, in crease in the level of resting calcium in single guinea-pig ventricula r myocytes. In particular, we wished to test the relative importance o f intracellular and extracellular sources of calcium in this phenomeno n. Methods: Carbon fibres were used to stretch cells loaded with the f luorescent calcium indicator Indo-1. Sarcomere length and internal cal cium activity ([Ca2+](i)) were measured. Experimental results from our present and previous studies were compared with those predicted by th e OXSOFT HEART (version 4) model of the guinea-pig ventricular myocyte incorporating a stretch-activated channel. Results: The stretch-induc ed increase in [Ca2+](i) was found to be sensitive to removal of [Ca2](0) and application of the Ca2+-channel blocker verapamil (1 mu M). T he phenomenon was not sensitive to disruption of sarcoplasmic reticulu m function by ryanodine (1 mu M) nor to the Na+ channel blocker TTX (3 0 mu M). Our experimental findings were reproduced in the modelling st udy. Conclusions: The stretch-induced increase in [Ca2+](i) is modulat ed by extracellular sources of Ca2+ rather than intracellular Ca2+ sto res and is not indiscriminately sensitive to blockers of depolarizing current. We propose that the stretch-induced increase in [Ca2+](i) may be triggered by activation of stretch-activated channels but that a c ombination of stretch-activated current and Ca2+-window current mainta in the increased levels of resting [Ca2+](i).