Studies on the role of Ttype calcium channels in the cardiovascular system using a specific inhibitor

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The T-type calcium channel has different properties and distribution for those of the L-type. It is considered to be involved in various physiological and pathophysiological phenomena such as cardiac automaticity, secretion of various active substances, and is therefore anticipated to be a novel therapeutic target. In the this project, I studied the physiological role of the T-type calcium channel using R (-) -efonidipine, the specific inhibitor I found in my previous studies. Contractile force experiments with isolated murine ventricular tissue revealed that the T-type calcium channel contributes to myocardial contraction in the fetal period but not at adulthood. Activation of the T-type calcium channel was involved in the endothelin- 1-induced positive inotropy. Microelectrode recordings in isolated sinoatrial-node preparations revealed that the T-type calcium channel is involved in the pacemaker depolarization of the mouse and guinea-pig but not in the rabbit, which agreed with earliler data on current density. This indicated that the different contribution of the T-type calcium current to pacemaking underlies species difference in heart rate. As it was shown that the factors which determines heart rate is different among species and the condition of the heart, extension of the present study to hearts from various pathological models may lead to the development of novel pharmacological therapy through regulation of heart rate.