Streptomycin and intracellular calcium modulate the response of single guinea-pig ventricular myocytes to axial stretch.
We tested the hypothesis that both stretch-activated channels (SACs) and intracellular calcium ([Ca(2+)](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, [Ca(2+)](i) transients or action potentials of electrically stimulated, unstretched myocytes, at a concentration of 50 microM, but at 40 microM, 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 microM streptomycin. However, exposure of cells to 5 microM BAPTA-AM, in order to reduce [Ca(2+)](i) transients, also abolished stretch-induced prolongation of the action potential. We conclude that both SACs and [Ca(2+)](i) are important in the electrical response of cardiac myocytes to stretch, and propose that stretch-induced changes in electrical activity and [Ca(2+)](i) may be linked by inter-dependent mechanisms.
Belus
Alexandra
A
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.
White
Ed
E
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006168:Guinea Pigs; D006352:Heart Ventricles; D007425:Intracellular Membranes / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology*; D010812:Physical Stimulation; D013307:Streptomycin / Q000494:pharmacology*
D002118:Calcium; D013307:Streptomycin