Effect of S16257 on L-type Calcium Current in Frog and Rat Ventricular Myocytes
Abstract
Myocardial ischaemia is often accompanied by increased heart rate (HR). Regular pharmacological agents used to reduce HR have an undesirable negative inotropic side-effect. For this reason the inhibitors of pacemaker current (I f) such as S16257 recently have been developed and are supposed to reduce HR selectively. We used whole-cell patch-clamp for studying the effect of S16257 on L-type Ca 2+ current (I Ca), which determines myocardial contraction force, in frog and rat ventricular myocytes. In frog ventricular myocytes 0.0010.01 mM of S16257 slightly stimulated (p > 0.05) I Ca , however, higher concentrations exerted a concentration-dependent inhibition of I Ca. Half concentration for inhibition (IC 50) was 0.41 mM. The peak of currentvoltage dependence curve was shifted from 0.1 ± 0.8 mV in control to 16.1 ± 1.6 mV in the presence of 1 mM of S16257. The inactivation of I Ca by 50% was obtained at 36.4 ± 1.3 mV in control and at 42.2 ± 0.9 mV in the presence of 1 mM of S16257. In rat ventricular myocytes 0.01 10 mM of S16257 exerted a concentration-dependent inhibition of I Ca. IC 50 was 0.52 mM. The peak of currentvoltage dependence curve was shifted from 1.6 ± 1.2 mV in control to 5.3 ± 0.9 mV in the presence of 1 mM of the compound. The inactivation of I Ca by 50% was obtained at 29.9 ± ± 1.0 mV in control and at 31.2 ± 1.0 mV in the presence of 1 mM of S16257. The effect of S16257 on I Ca in both species was completely reversible. The results show that in frog and rat ventricular myocytes S16257 at concentrations higher than 0.01 mM exert a concentration-dependent dihydropyridine-antagonists-like inhibitory effect on I Ca. This inhibitory effect is dependent on the membrane potential only in frog ventricular myocytes.
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