Cardiovascular T-type calcium channels: Physiological and pharmacological significance

Cellular calcium regulation. A variety of Ca²⁺ control processes are responsible for Ca²⁺ homeostasis and signaling. Voltage-gated Ca²⁺ channels are dominant in the cardiovascular system. Voltage-gated Ca²⁺ channels. There are several distinct subclasses of Ca²⁺ channels, distinguished by location, biophysical, structural and pharmacological characteristics. They include both high- and low-voltage-activated channels. The long-lasting (L) type of high-voltage-activated channel is well characterized and is the site of action for the existing clinically available Ca²⁺ channel antagonists: nifedipine, verapamil and diltiazem. T-type Ca²⁺ channels. The low-voltage-activated transient (T-type) channel is widespread in the cardiovascular system and in neurons. It serves pacemaking functions and supports Ca²⁺ signaling in secretory cells and vascular smooth muscle. The T-type channel also functions in cell growth processes under physiological and pathological conditions. Mibefradil as a T-type Ca²⁺ channel antagonist. Mibefradil (Ro 40-5967) is a structurally novel Ca²⁺ antagonist with selectivity for T-type over L-type channels. This selectivity may underlie its vasodilating activity and heart rate depressive effect, its lack of negative inotropy and its cardioprotective properties.