Adenosine-activation of voltage-dependent K+ currents

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DESCRIPTION (provided by applicant): Potassium channel activation has been identified as an important component of adenosine-mediated relaxation in the coronary microcirculation. We have recently provided the first evidence for significant voltage-dependent (Kv) K+ channel contribution to ADO-mediated relaxation in porcine coronary arterioles. Our subsequent studies reveal that hypercholesterolemia abolishes the Kv channel contribution to ADO-mediated relaxation. Therefore, the primary objectives are to determine the Kv channel isoforms activated by ADO and the effect of hypercholesterolemia on these isoforms. Two specific aims will be addressed: Aim #1 will determine the Kv channel isoforms that contribute to ADO-activation of whole-cell K+ current in coronary arteriolar smooth muscle cells. Aim #2 will determine the expression of candidate Kv channel isoforms in coronary arteriolar smooth muscle from control and hypercholesterolemic animals. The overall hypothesis of this research proposal is that hypercholesterolemia alters the Kv channel isoforms present in the coronary microcirculation such that those that contribute to ADO-mediated relaxation are no longer expressed.