grantor:
University of TorontoIschemic preconditioning (IP) is a cardioprotective phenomenon potentially mediated through multiple signal transduction pathways. Given the importance of chloride (Cl-) channels in cell volume regulation and the disordered cell volume regulation known to occur in ischemia/reperfusion injury, together with the need to maintain electroneutrality via an efflux of potassium ions (K+) via the inward rectifier potassium channel (IK1), I hypothesize that Cl-- and IK 1 channels are end-effectors of IP. Pharmacological preconditioning by direct activation of angiotensin II AT1 and adenosine A 1/A3 receptors and by stimulation of PKC was abolished by Cl- channel inhibition in both the isolated rabbit ventricular myocyte and buffer-perfused whole heart model. In addition, IK1 channel inhibition blocked the protection induced by IP, hypo-osmotic stress and of angiotensin AT1 receptor activation. These results support the hypothesis that CI- and IK1 channels act as end-effectors of ischemic preconditioning.M.Sc
