ATP-Sensitive Potassium Channels in the Cerebral Circulation

Abstract

Background— In brain blood vessels, electrophysiological studies proving the existence of ATP-sensitive potassium channels (K _ATP ) are scarce. However, numerous pharmacological studies establish the importance of K _ATP channels in these blood vessels. This review emphasizes the data supporting the importance of vascular K _ATP in the responses of brain blood vessels. Summary of Review— Electrophysiological data show the existence of K _ATP in smooth muscle and endothelium of brain vessels. A much larger number of studies in virtually all experimental species have shown that classic openers of K _ATP dilate brain arteries and arterioles. This response can by blocked by glibenclamide, a selective inhibitor of K _ATP opening. Several physiological or pathophysiological responses are also blocked by glibenclamide. K _ATP contains a multiplicity of potential sites of interaction with drugs of diverse, sometimes unrelated, structures. Drugs with imidazole or guanidinium groups are particularly likely to have effects on K _ATP . This complicates interpretation of the actions of such drugs when used as supposedly selective pharmacological probes for other putative targets. A pH-sensitive site on the internal surface of cloned channels may explain the glibenclamide-inhibitable dilation produced by intracellular acidosis and perhaps by CO ₂ . In some situations K _ATP appears to be involved in either the synthesis/release or action of endothelium-derived mediators of cerebrovascular tone. The importance of K _ATP may be dependent on the portion of the cerebrovascular tree being studied and on diverse experimental conditions, age, species, and the presence of disease. Conclusions— K _ATP have been shown to mediate a wide range of cerebrovascular response in physiologic or pathologic circumstances in a variety of experimental conditions. Their relevance to cerebrovascular responses in humans remains to be explored.