Potassium Channel Opening and Coronary Vasodilation by Halothane

Publisher Summary This chapter discusses the studies on halothane vasodilation in the presence and absence of glyburide or 5-hydroxydecanoate (5-HD), pharmacological blockers of ATP-sensitive K+ channels (K ATP ) to establish whether halothane relaxes intact epicardial coronary arteries by opening vascular smooth muscle (VSM) K + channels. Halothane is known to be a less effective vasodilator during high-K + coronary contraction than with receptor agonist-induced precontraction. Alternatively, halothane could directly decrease Ca 2+ influx through Ca 2+ channels. It is observed that halothane vasodilation of K + -contracted epicardial coronary VSM, in the absence of agonists or other stimuli, does not involve processes sensitive to the transsarcolemmal K + gradient or membrane potential. This finding is not consistent with halothane possessing either a K + channel- or a voltage-sensitive Ca 2+ channel-dependent mechanism. It implies that the vasodilator effect of halothane under these conditions may be mediated by other intracellular processes, such as the inositol trisphosphate (IP 3 )-regulated sarcoplasmic reticulum (SR) Ca 2+ release channel or non-Ca 2+ -dependent processes that regulate myosin light chain phosphorylation and contraction, such as protein kinase C. It is also observed that cyclooxygenase blockade with indomethacin abolishes halothane vasodilation, both in the presence and absence of glyburide. Other notable findings from this study include the observation that 100 μM 5-HD that is reported to completely inhibit K ATP channels of cardiomyocytes, did not attenuate cromakalim vasodilation. This suggests that 5-HD is not an effective blocker of K ATP channels in VSM preparations.