Chloride channels and their functional roles in smooth muscle tone in the vasculature

Although evidence of important contributions by Cl- channels to agonist-induced currents have been reported in vascular smooth muscle cells, the functional roles played by Cl- channels in the smooth muscle contraction and in setting the membrane potential remain essentially obscure. All of the admittedly few papers published have focused on the physiological roles of Cl- channels in the contraction and membrane depolarization elicited by agonists. At present, it seems likely that in vascular cells: a) Cl- conductance contributes to membrane depolarization, with the subsequent contraction being due to Ca2+ release from the intracellular store sites, and b) Cl- movements through the membrane of the Ca2+ store sites also regulate Ca2+ release and Ca2+ uptake from/into the store sites. As a Ca2+-dependent Cl- current is most easily demonstrated under quasi-physiological conditions (by the perforated patch-clamp method), the contribution made by Cl- channels to smooth muscle function may be more important than previously thought. The development of the new, selective Cl--channel blockers as well as the identification and gene engineering of the channel molecules are essential if we are to advance our knowledge of the physiology and pharmacology of the Cl- channels residing in vascular smooth muscle cells.