Transport and function of chloride in vascular smooth muscles

Abstract

This review summarizes the current knowledge of Cl(-) transport in vascular smooth muscle cells (VSMCs). VSMCs accumulate Cl(-) intracellularly using two secondary-active transport mechanisms. The Cl(-) equilibrium potential is more positive than the resting membrane potential enabling Cl(-) to be a depolarizing ion upon activation of a Cl(-) conductance. Cl(-) currents are involved in different vascular responses suggesting a number of different Cl(-) channels. All known Cl(-) channel families, with the exception of the GABA-/glycine-receptor family, have been identified in VSMCs. At least one member of the voltage-activated ClC family - ClC-3 - has been suggested to be involved in myogenic constriction, in cell proliferation and to have an anti-apoptotic action. The cystic fibrosis transmembrane conductance regulator is also demonstrated in VSMCs. The molecular identity of the major anion conductance in VSMCs - a Ca(2+)-activated Cl(-) current - is uncertain. Several candidates have been suggested with bestrophin and TMEM16 protein families the current favorites. Specific pharmacological tools are lacking for Cl(-) channels but recent molecular biology developments have made selective gene manipulations possible. A continuing quest within the vascular research field is to explicitly demonstrate the coupling between a putative channel protein and an endogenous Cl(-) current and the importance of these for specific functions.