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

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American Physiological Society

RESUMO

Two-pore domain K+ (K2P) channels are a new channel family. The goal of this study was to determine if K2P channels are activated by the nitric oxide (NO)/cGMP/PKG pathway in vascular smooth muscle. Relative levels of message for K2P 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 K2P channels. Message for TREK-1 was the most abundant K2P channel, followed by TASK-1 and TWIK-2, which were expressed at ∼10% of the level of TREK-1. Message for other K2P channels was 1% or less than that of TREK-1. A number of K2P 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 K2P channels are resistant to the blocking effects of TEA, we conclude that K2P channels in vascular smooth muscle were not activated by the NO/cGMP/PKG pathway. Although K2P channels are highly expressed, K2P currents are not activated via the NO/cGMP pathway in rat MCA smooth muscle, despite the presence of numerous putative PKG phosphorylation sites.

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