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

ABSTRACT: 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 approximately 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 muM) or the membrane permeable analog of cGMP 8-bromo-cGMP (10 muM) elicited transient increases in whole cell current of vascular smooth muscle from the rat MCA. However, after large-conductance Ca(2+)-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.

SUBMITTER: Lloyd EE

PROVIDER: S-EPMC2716098 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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

Lloyd Eric E EE Marrelli Sean P SP Bryan Robert M RM

American journal of physiology. Heart and circulatory physiology 20090410 6

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 th ...[more]

PMID: 19363137

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Project description:Constitutively active background or "leak" two-pore-domain potassium (K(+)) channels (Kcnk family), as defined by lack of voltage and time dependency are central to electrical excitability of cells by controlling resting membrane potential and membrane resistance. Inhibition of these channels by several neurotransmitters, e.g. glutamate, or acetylcholine, induces membrane depolarization and subsequent action potential firing as well as increases membrane resistance amplifying responses to synaptic inputs. In contrast, their opening contributes to hyperpolarization. Because of their central role in determining cellular excitability and response to synaptic stimulation, these channels likely play a role in the differential effects of vestibular efferent neurons on afferent discharge. Microarray data from previous experiments showed Kcnk 1, 2, 3, 6, 12 and 1 5 mRNA in Scarpa's ganglia. Real-time RT-PCR showed Kcnk 1, 2, 3, 6, 12 and 15 mRNA expression in Scarpa's ganglia and Kcnk 1, 2, 3, 6, 12 but not 15 mRNA expression in the crista ampullaris. We studied the distribution of two-pore-domain potassium channels K(2P)1.1, 2.1, 3.1 and 6.1 like immunoreactivity (corresponding to Kcnk genes 1, 2, 3 and 6) in the vestibular periphery. K(2P)1.1 (TWIK 1) immunoreactivity was detected along nerve terminals, supporting cells and blood vessels of the crista ampullaris and in the cytoplasm of neurons of the Scarpa's ganglia. K(2P)2.1 (TREK 1) immunoreactivity was detected in nerve terminals and transitional cells of the crista ampullaris, in the vestibular dark cells and in neuronal fibers and somata of neurons of Scarpa's ganglia. K(2P)3.1 (TASK 1) immunoreactivity was detected in supporting cells and transitional cells of the crista ampullaris, in vestibular dark cells and in neuron cytoplasm within Scarpa's ganglia. K(2P)6.1 (TWIK 2) immunoreactivity was detected in nerve terminals, blood vessels hair cells and transitional cells of the crista ampullaris and in the somata and neuron fibers of Scarpa's ganglia.

Dataset Information

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

Publications

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

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