Vascular Physiology and Ion Channel Function
Research in my laboratory focuses on the endothelium-mediated regulation of vascular smooth muscle contractility and the roles of calcium-activated potassium (K+) channels in these processes. Three main classes of calcium-activated K+ channels have been identified, and are typically referred to as large, intermediate and small conductance channels (BKCa, IKCa and SKCa channels, respectively), based on their biophysical properties. The ability of these channels to open in response to changes in membrane voltage and/or cytosolic free calcium allows them to function as feedback regulators of cellular processes that depend upon depolarization-induced elevations of intracellular calcium (e.g. muscle contraction, gene expression, secretion of neurotransmitters and hormones). Our current research interests include: 1) the contribution of IKCa and SKCa K+ channels to endothelial function and the regulation of myogenic tone in resistance arteries, 2) the modulation of smooth muscle BKCa channel activity by endothelium via the nitric oxide/cGMP signaling pathway and 3) the in vivo actions of KCa channel modifying drugs on the cardiovascular system. Experimentally, we utilize patch clamp electrophysiology, fluorescence-based measurements in isolated cells, arterial pressure myography and numerous biochemical techniques (e.g. western blot, Q-PCR) to investigate vascular function at multiple levels. Some of our current interests focus on endothelial dysfunction in the setting of Type 2 Diabetes.