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We tested the hypothesis that both stretch-activated channels (SACs) and intracellular calcium ([Ca2+]i) are important in the electrical response of single guinea-pig ventricular myocytes to axial stretch. Myocytes were attached to carbon fibre transducers and stretched, sarcomere length increased by approximately 9 %, and there was a prolongation of the action potential duration. Streptomycin, a blocker of SACs, had no effect upon the shortening, [Ca2+]i transients or action potentials of electrically stimulated, unstretched myocytes, at a concentration of 50 µM, but at 40 µM, prevented any stretch-induced increase in action potential duration. Under action potential clamp, stretch elicited a current with a linear current-voltage relationship that was inward at membrane potentials negative to its reversal potential of -30 mV, in 10 of 24 cells tested, and was consistent with the activation of non-specific, cationic SACs. This current was not seen in any stretched cells that were exposed to 40 µM streptomycin. However, exposure of cells to 5 µM BAPTA-AM, in order to reduce [Ca2+]i transients, also abolished stretch-induced prolongation of the action potential. We conclude that both SACs and [Ca2+]i are important in the electrical response of cardiac myocytes to stretch, and propose that stretch-induced changes in electrical activity and [Ca2+]i may be linked by inter-dependent mechanisms.
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