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Inotropic effects of MCI-154 on rat cardiac myocytes

Chen Huanzhen, Cui Xiangli, Zhao Huachen, Zhao Luying, Lu Jiyuan, Wu Bowei

Department of Physiology, Shanxi Medical University. Taiyuan 030001, China

Abstract

Calcium sensitizers exert positive inotropic effects without increasing intracellular Ca~(2+). Thus, they avoid the undesired effects of Ca~(2+) overload such as arrhythmias and cell injury, but most of them may impair myocyte relaxation. However, MCI-154, also a calcium sensitizer, has no impairment to cardiomyocyte relaxation. To clarify the underlying mechanisms, we examined the effects of MCI-154 on Ca~(2+) transient and cell contraction usingion imaging system, and its influence on L-type Ca~(2+) current and Na+/Ca~(2+) exchange current with patch clamp technique in rat ventricular myocytes as well. The results showed that: (1) MCI-154 (1～100 #mu#mol/L) had no effect on L-type Ca~(2+) current; (2) MCI-154 concentration-dependently increased cell shortening from 5.00±1.6 #mu#m of control to 6.2±1.6 #mu#m at 1 #mu#mol/L,8.7±1.6 #mu#m at 10 #mu#mol/L and 14.0±1.4 #mu#m at 100 #mu#mol/L, respectively, with a slight increase in Ca~(2+) transient amplitude and an abbreviation of Ca~(2+) transient restore kinetics assessed by time to 50% restore (TR50) and time to 90% restore (TR90); (3) MCI-154 dosedependently increased the electrogenic Na+/Ca~(2+) exchange current both in the inward and the outward directions in rat ventricular myocytes. These results indicate that MCI-154 exerted a positive inotropic action without impairing myocyte relaxation. The stimulation of inward Na+/Ca~(2+) exchange current may accelerate the Ca~(2+) effiux, leading to abbreviations of TR_(50) and TR_(90) in rat myocytes. The findings suggest that the improvement by MCI-154 of myocyte relaxation is attributed to the forward mode of Na+/Ca~(2+) exchange.

Key words: MCI-154;;Calcium sensitizer;;Fura-2;;Calcium transient;

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Citing This Article：

Chen Huanzhen, Cui Xiangli, Zhao Huachen, Zhao Luying, Lu Jiyuan, Wu Bowei. Inotropic effects of MCI-154 on rat cardiac myocytes. Acta Physiol Sin 2004; 56 (3): (in Chinese with English abstract).