Andrew Braun

Ion channels are the fundamental membrane particles that underlie cellular excitability by both initiating and transducing electrical signals between cells. Research in my laboratory focuses on the regulation of blood flow and blood pressure by resistance arteries, and the vasoactive signaling mechanisms (e.g. nitric oxide release, electrical coupling and membrane hyperpolarization) underlying endothelium-dependent modulation of vascular smooth muscle contractility. We are particularly interested in calcium-activated K+ (KCa) channels expressed in both vascular endothelium and smooth muscle, which are critically involved in these processes. Pharmacologic manipulation of these channels is able to evoke either arterial dilation or constriction, and can be targeted to restore normal vascular function in resistance arteries from type 2 diabetic rats and patients. Early pre-clinical data from our group suggests that long-term pharmacologic enhancement of endothelial KCa channel activity in vivo can improve the cardiovascular disease profile in type 2 diabetic rats. KCa channels in the vascular wall may thus represent a novel therapeutic target for reducing the onset and/or severity of endothelial dysfunction and vascular disease in conditions such as hypertension, atherosclerosis and coronary artery disease. Our current research interests include: 1) the regulation of large conductance, BK-type channels in arterial smooth muscley by endothelium via the nitric oxide/cGMP signaling pathway; and 2) the regulation of myogenic tone in small resistance arteries by endothelial KCa channels (i.e. SKCa and IKCa channels); 3) the effects of small molecule, endothelial KCa channel activators and inhibitors on cardiovascular function in whole tissues and animals following acute and long-term administration.
Experimentally, we utilize patch clamp methodologies and live cell fluorescence imaging to examine ion channel activity and intracellular calcium dynamics to investigate signaling mechanisms in isolated vascular cells. Arterial pressure myography is used to investigate endothelium-dependent regulation of myogenic contractility in isolated resistance arteries, and Langendorff perfusion techniques in isolated beating hearts is utilized to interrogate the regulation of the intact coronary circulation. Echocardiography combined with the surgical implantation of radio-telemeter, allows us to monitor in vivo cardiac structure/function, blood pressure and heart rate in healthy and diseased animal models to determine the impact of endothelial KCa channel modulators on whole body function and cardiovascular performance.

Administrative Assistant

Theresea Connolly
tconnoll@ucalgary.ca
403-220-3018