This Article Full Text Full Text (PDF) All Versions of this Article: 34/6/1547    most recent 01.STR.0000070425.98202.B5v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rosenblum, W. I. Search for Related Content PubMed PubMed Citation Articles by Rosenblum, W. I. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Ion channels/membrane transport Brain Circulation and Metabolism Other Vascular biology

(Stroke. 2003;34:1547.)
© 2003 American Heart Association, Inc.

Comments, Opinions, and Reviews

ATP-Sensitive Potassium Channels in the Cerebral Circulation

From the Department of Pathology, Division of Autopsy and Neuropathology, Virginia Commonwealth University, Medical College of Virginia, Richmond, Va.

Correspondence to William I. Rosenblum, MD, 305 Tarrytown Dr, Richmond, VA 23229. E-mail wirosenb{at}aol.com

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 CO₂. 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.

Key Words: adenosine triphosphate • aging • autoregulation • biological factors • carbon dioxide • cerebral circulation • diabetes mellitus • endothelium-derived relaxing factor • endothelium, vascular • enzyme inhibitors • hydrogen-ion concentration • hypertension • hypoxia • nitric oxide synthase • potassium channels • vasodilation

This article has been cited by other articles:

				A. Adebiyi, E. M. McNally, and J. H. Jaggar Sulfonylurea Receptor-Dependent and -Independent Pathways Mediate Vasodilation Induced by ATP-Sensitive K+ Channel Openers Mol. Pharmacol., September 1, 2008; 74(3): 736 - 743. [Abstract] [Full Text] [PDF]

				Y. Shi, Z. Wu, N. Cui, W. Shi, Y. Yang, X. Zhang, A. Rojas, B. T. Ha, and C. Jiang PKA phosphorylation of SUR2B subunit underscores vascular KATP channel activation by beta-adrenergic receptors Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1205 - R1214. [Abstract] [Full Text] [PDF]

				C. W. Leffler, H. Parfenova, J. H. Jaggar, and R. Wang Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation J Appl Physiol, March 1, 2006; 100(3): 1065 - 1076. [Abstract] [Full Text] [PDF]

				H. Tomura, J.-Q. Wang, M. Komachi, A. Damirin, C. Mogi, M. Tobo, J. Kon, N. Misawa, K. Sato, and F. Okajima Prostaglandin I2 Production and cAMP Accumulation in Response to Acidic Extracellular pH through OGR1 in Human Aortic Smooth Muscle Cells J. Biol. Chem., October 14, 2005; 280(41): 34458 - 34464. [Abstract] [Full Text] [PDF]