Role of T channels in cardiovascular function.

Although two types of Ca2+ channels are found to occur in the cardiovascular system, very little is known about one of them, primarily because a pharmacological blocking agent has been lacking. The enigmatic transient (T)-type Ca2+ channel has finally been recognized by a selective Ca2+ antagonist. The novel tetralol Ca2+ antagonist, mibefradil, is a selective T-type Ca2+ channel blocker that produces effective vasodilatation with additional inhibitory actions on blood vessel wall and left ventricular thickening. The availability of a blocking agent has begun to reveal the significance of T-type Ca2+ channel signals. Selective T-type Ca2+ channel blockade characteristics include vascular selectivity, freedom from negative cardiac inotropism, consistent and predictable reduction in heart rate, reduction in subendothelial proliferation, and increased survival of severely hypertensive and heart failure animal models. Mibefradil increases coronary blood flow without increasing myocardial oxygen consumption, and by decreasing heart rate and thus time spent in diastole, improves subendocardial perfusion. Improved perfusion of the myocardial wall and lowered heart rate appear to normalize the underlying pathophysiological factors, improve heart failure, and provide long-term protection. Thus, T-type Ca2+ channel blockade offers significant new cardiovascular protective benefits, even in the presence of critical pathophysiological elements (i.e. increased heart rate and neurohumors in the presence of decreased ejection fraction and contractility) found in heart failure.