Ca2+ entry channels involved in endothelin-1-induced contractions of vascular smooth muscle cells.

Endothelin-1 (ET-1) is a 21-amino-acid peptide and it is one of the most potent endogenous vasoconstricting agent yet discovered (Yanagisawa et al., 1988). ET-1 binds to its receptors (typically ETA receptor) on vascular smooth muscle cells (VSMCs) and subsequently induces an increase in the intracellular free Ca2+ concentration ([Ca]i), which is essential for contraction of the cells. It is generally accepted that the major part of the ET-1-induced sustained contractions and increases in [Ca]i requires the persistent entry of extracellular Ca2+ (Rubanyi and Polokoff, 1994; Komuro et al., 1997; Zhang et al., 1998). The earlier studies with patch-clamp technique have shown that voltage-operated Ca2+ channel (VOCC) is activated by ET-1 in VSMCs from porcine coronary artery (Goto et al., 1989) and guinea-pig portal vein (Inoue et al., 1990). However, subsequent studies showed that ET-1-induced contractions (Chabrier et al., 1989; D’Orleans-Juste et al., 1989; Turner et al., 1989; Nakajima et al., 1996; Komuro et al., 1997) and increases in [Ca]i (Huang et al., 1990; Takuwa et al., 1990; Zhang et al., 1998) are virtually resistant to specific blockers of L-type VOCC such as nifedipine which completely suppress the contractions induced by depolarization with high K+ stimulation. Thus it is now considered that the ET-1-induced contractions and increases in [Ca]i depend mainly on Ca2+ entry through channels other than VOCC. However, it is totally unknown what types of Ca2+ entry channel are involved in the contractions and increases in [Ca]i induced by ET-1. This review focuses on the recent development of Ca2+ entry channels in VSMCs activated by ET-1.