STREPTOMYCIN REVERSES A LARGE STRETCH-INDUCED INCREASE IN [CA2+](I) IN ISOLATED GUINEA-PIG VENTRICULAR MYOCYTES

Objective: The aim was to test the hypothesis that in single guinea pig ventricular myocytes a large stretch induced increase in resting calcium was sensitive to the mechanosensitive channel blocker streptomycin. Methods: Carbon fibres were used to stretch cells loaded with the fluorescent calcium indicator indo-1. Force, sarcomere length, and internal calcium activity ([Ca2+](i)) were measured. Results: In approximately 60% of the cells studied, a stretch which increased sarcomere length by approximately 6% caused a large increase in [Ca2+](i) (up to 60% of the size of a [Ca2+](i) transient at 0.25 Hz). When a mixture of antibiotics (streptomycin-penicillin) was used in solutions to isolate and store cells, this phenomenon was never observed (n = 19 cells). Direct application of physiological saline solution (PSS) could not reverse the increase in [Ca2+](i) within 60 s of application (n = 7 cells). Direct application of penicillin [1000 IU per 50 ml (40 mu M)] reversed the increase in [Ca2+](i) within 60 s of application in only 3/7 cells. In contrast direct application of the aminoglycoside antibiotic streptomycin (40 mu M) rapidly reversed the large increase in [Ca2+](i) induced by stretch in each of 13 cells [within 18(SD 10) s of application]. Acute application of 40 mu M streptomycin did not modify L-type Ca2+ currents measured under whole cell patch clamp conditions. Measurement of the resting tension - sarcomere length curves in cells stored in solution containing streptomycin and penicillin revealed two populations of cells on the basis of their stiffness. Conclusions: This stretch induced increase in [Ca2+]i may be associated with stretch activated arrhythmias in the heart. The effects of streptomycin are consistent with its reported inhibitory action on stretch activated channels.