Abstract 16586: The Intermediate-Conductance Ca2+-activated K+ Channel KCa3.1 Regulates Proliferation of Human Coronary Smooth Muscle Cells

Introduction: Vascular smooth muscle cell (VSMC) proliferation is a pathological process occurring in vascular remodeling. We have previously demonstrated that the intermediate-conductance Ca2+-activated K+ channel KCa3.1 is upregulated in proliferating VSMCs, and the blockade, knockdown and deficiency of KCa3.1 suppress VSMC proliferation. Here we further explored the mechanism by which KCa3.1 regulates VSMC proliferation. Methods and Results: Platelet-derived growth factor-BB (PDGF, 20 ng/ml)-induced proliferation (using a BrdU incorporation assay) of human coronary artery VSMCs was attenuated by lowering intracellular Ca2+ concentration ([Ca2+]i) with BAPTA (30 μ M, an intracellular Ca2+ chelator) and was enhanced by a forced rise in [Ca2+]i with A23187 (0.1 to 1 nM, a Ca2+ ionophore). KCa3.1 blockade with TRAM-34 (100 nM, a specific blocker of KCa3.1) or siRNA knockdown reduced proliferation by inhibiting the rise in [Ca2+]i, as assessed in fluorescence microscopy with Fluo-4 (a Ca2+-sensitive dye), a...