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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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Submitted on : Monday, March 21, 2022 - 5:56:03 PM
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V Skeberdis, Jonas Jurevièius, Rodolphe Fischmeister. Effect of S16257 on L-type Calcium Current in Frog and Rat Ventricular Myocytes. Acta Medica Lituanica, Vilnius University Press, 2002, 9 (1), pp.69-75. ⟨hal-03610243⟩

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