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 microM) 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 microM) 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 microM 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.