Effects of streptomycin sulphate on I(CaL), I(Kr) and I(Ks) in guinea-pig ventricular myocytes.
In single guinea pig ventricular myocytes, streptomycin sulphate (streptomycin) reduced intracellular Ca(2+) transients (IC(50) 1.9 mM) and contractility (IC(50) 1.0 mM), 2 mM streptomycin prolonged the action potential. Under switch voltage clamp, 2 mM streptomycin reduced the L-type Ca(2+) current (I(CaL)) amplitude and (Ca(2+)-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 Ca(2+)-dependent, not being seen when nifedipine and BAPTA were used to reduce intracellular Ca(2+). 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 Ca(2+) 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.
Belus
Alexandra
A
School of Biomedical Sciences, University of Leeds, UK.
White
Ed
E
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology*; D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D013307:Streptomycin / Q000494:pharmacology*; D016276:Ventricular Function
D020746:Calcium Channels, L-Type; D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C059983:potassium channel protein I(sk); D002118:Calcium; D013307:Streptomycin