Effects of streptomycin sulphate on ICaL, IKr and IKs in guinea-pig ventricular myocytes

In single guinea pig ventricular myocytes, streptomycin sulphate (streptomycin) reduced intracellular Ca2+ transients (IC50 1.9 mM) and contractility (IC50 1.0 mM), 2 mM streptomycin prolonged the action potential. Under switch voltage clamp, 2 mM streptomycin reduced the L-type Ca2+ current (I-CaL) amplitude and (Ca2+-dependent) relative inactivation at positive membrane potentials and reduced the rapid and slow components of the delayed rectifier current (I-K). This latter effect seemed Ca2+-dependent, not being seen when nifedipine and BAPTA were used to reduce intracellular Ca2+. Fifty micromolars of streptomycin had no significant effects on any parameter studied. We conclude that the negative inotropic effect of streptomycin results from blockade of I-CaL, and thus, a reduction of intracellular Ca2+ transients, while prolongation of the action potential is more consistent with effects on I-K. These observations link mechanical and electrical effects of streptomycin that may be important, for example, when streptomycin is used to block stretch-activated events in cardiac muscle. (C) 2002 Elsevier Science B.V All rights reserved.