Regulation of ion channels in smooth muscles by calcium

Intracellular Ca2+ concentration ([Ca2+]i) plays a central role in regulating tone and contractility of smooth muscle cells. In contrast to the "classic" model of electromechanical coupling where membrane potential determines [Ca2+]i, it is now well established that [Ca2+]i in turn may also affect membrane potential by modulating open probabilities of ion channels. Activation by [Ca2+]i of large-conductance K+ channels, Cl- channels, and nonselective cation channels has been described, as well as block of delayed rectifier K+ channels by [Ca2+]i and [Ca2+]i-induced inactivation of Ca2+ channels. Therefore, a network consisting of positive- and negative-feedback loops regulates [Ca2+]i as well as membrane potential. In this context, we review the properties of Ca(2+)-dependent ion channels and their functional role in vascular and visceral smooth muscles. Any alteration of the "Ca2+ sensitivity" of ion channels is expected to have a profound effect on the reciprocal relationship between membrane potential and [Ca2+]i. Already several molecular factors determining Ca2+ sensitivity of Ca(2+)-activated K+ channels have been identified. We provide a working definition for Ca2+ sensitivity.