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This Article Full Text Full Text (PDF) All Versions of this Article: 296/6/H1774    most recent 00082.2009v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Lloyd, E. E. Articles by Bryan, R. M. PubMed PubMed Citation Articles by Lloyd, E. E. Articles by Bryan, R. M., Jr.

cGMP does not activate two-pore domain K⁺ channels in cerebrovascular smooth muscle

¹Cerebrovascular Research Laboratory, Department of Anesthesiology, ²Department of Molecular Physiology and Biophysics, and ³Department of Medicine (Cardiovascular Sciences), Baylor College of Medicine, Houston, Texas

Submitted 23 January 2009 ; accepted in final form 5 April 2009

Two-pore domain K⁺ (K_2P) channels are a new channel family. The goal of this study was to determine if K_2P channels are activated by the nitric oxide (NO)/cGMP/PKG pathway in vascular smooth muscle. Relative levels of message for K_2P channels were assessed in rat middle cerebral arteries (MCAs) using quantitative RT-PCR, and K⁺ currents were measured in freshly dispersed vascular smooth muscle cells of the MCA. The rat MCA expresses a number of K_2P channels. Message for TREK-1 was the most abundant K_2P channel, followed by TASK-1 and TWIK-2, which were expressed at 10% of the level of TREK-1. Message for other K_2P channels was 1% or less than that of TREK-1. A number of K_2P channels, including TREK-1, TWIK-2, and TASK-1, have putative PKG phosphorylation sites in the intracellular domains. The NO donor sodium nitroprusside (100 µM) or the membrane permeable analog of cGMP 8-bromo-cGMP (10 µM) elicited transient increases in whole cell current of vascular smooth muscle from the rat MCA. However, after large-conductance Ca²⁺-activated K⁺ channels had been blocked with 10 mM tetraethylammonium (TEA), no increase in whole cell current was observed. Since K_2P channels are resistant to the blocking effects of TEA, we conclude that K_2P channels in vascular smooth muscle were not activated by the NO/cGMP/PKG pathway. Although K_2P channels are highly expressed, K_2P currents are not activated via the NO/cGMP pathway in rat MCA smooth muscle, despite the presence of numerous putative PKG phosphorylation sites.

cerebrovascular circulation; nitric oxide/cGMP/protein kinase G; vasodilation