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Br J Pharmacol
2012 Jun 01;1664:1377-87. doi: 10.1111/j.1476-5381.2012.01863.x.
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Pharmacological dissection of K(v)7.1 channels in systemic and pulmonary arteries.
Chadha PS
,
Zunke F
,
Davis AJ
,
Jepps TA
,
Linders JT
,
Schwake M
,
Towart R
,
Greenwood IA
.
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BACKGROUND AND PURPOSE: The aim of this study was to characterize the functional impact of KCNQ1-encoded voltage-dependent potassium channels (K(v)7.1) in the vasculature.
EXPERIMENTAL APPROACH: Mesenteric arteries, intrapulmonary arteries and thoracic aortae were isolated from adult rats. K(v)7.1 channel expression was established by fluorescence immunocytochemistry. Wire myography determined functionality of these channels in response to selective blockers and activators. Xenopus oocytes expressing K(v)7.1 channels were used to assess the effectiveness of selective K(v)7.1 channel blockers.
KEY RESULTS: K(v)7.1 channels were identified in arterial myocytes by immunocytochemistry. K(v)7.1 blockers HMR1556, L-768,673 (10 µM) and JNJ39490282 (JNJ282; 1 µM) had no contractile effects in arteries, whereas the pan-K(v)7 channel blocker linopirdine (10 µM) evoked robust contractions. Application of two compounds purported to activate K(v)7.1 channels, L-364 373 (R-L3) and mefenamic acid, relaxed mesenteric arteries preconstricted by methoxamine. These responses were reversed by HMR1556 or L-768,673 but not JNJ282. Similar effects were observed in the thoracic aorta and intrapulmonary arteries.
CONCLUSIONS AND IMPLICATIONS: In contrast to previous assumptions, K(v)7.1 channels expressed in arterial myocytes are functional ion channels. Although these channels do not appear to contribute to resting vascular tone, K(v)7.1 activators were effective vasorelaxants.
Alexander,
Guide to Receptors and Channels (GRAC), 5th edition.
2011, Pubmed
Alexander,
Guide to Receptors and Channels (GRAC), 5th edition.
2011,
Pubmed
Antzelevitch,
Ionic, molecular, and cellular bases of QT-interval prolongation and torsade de pointes.
2007,
Pubmed
Barhanin,
K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current.
1996,
Pubmed
,
Xenbase
Bentzen,
The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels.
2006,
Pubmed
,
Xenbase
Bett,
Ancillary subunits and stimulation frequency determine the potency of chromanol 293B block of the KCNQ1 potassium channel.
2006,
Pubmed
,
Xenbase
Busch,
Positive regulation by chloride channel blockers of IsK channels expressed in Xenopus oocytes.
1994,
Pubmed
,
Xenbase
Busch,
The role of the IsK protein in the specific pharmacological properties of the IKs channel complex.
1997,
Pubmed
,
Xenbase
Davis,
Expression profile and protein translation of TMEM16A in murine smooth muscle.
2010,
Pubmed
Greenwood,
Comparison of the effects of fenamates on Ca-activated chloride and potassium currents in rabbit portal vein smooth muscle cells.
1995,
Pubmed
Greenwood,
New tricks for old dogs: KCNQ expression and role in smooth muscle.
2009,
Pubmed
Grunnet,
KCNE4 is an inhibitory subunit to Kv1.1 and Kv1.3 potassium channels.
2003,
Pubmed
,
Xenbase
Gögelein,
Inhibition of IKs channels by HMR 1556.
2000,
Pubmed
,
Xenbase
Herbert,
KCNQ1 gene mutations and the respective genotype-phenotype correlations in the long QT syndrome.
2002,
Pubmed
Jepps,
Downregulation of Kv7.4 channel activity in primary and secondary hypertension.
2011,
Pubmed
Jespersen,
The KCNQ1 potassium channel: from gene to physiological function.
2005,
Pubmed
Joshi,
Pulmonary vasoconstrictor action of KCNQ potassium channel blockers.
2006,
Pubmed
Joshi,
KCNQ modulators reveal a key role for KCNQ potassium channels in regulating the tone of rat pulmonary artery smooth muscle.
2009,
Pubmed
Kang,
Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel.
2008,
Pubmed
Knollmann,
Kcnq1 contributes to an adrenergic-sensitive steady-state K+ current in mouse heart.
2007,
Pubmed
Lerche,
Chromanol 293B binding in KCNQ1 (Kv7.1) channels involves electrostatic interactions with a potassium ion in the selectivity filter.
2007,
Pubmed
,
Xenbase
Lerche,
Molecular impact of MinK on the enantiospecific block of I(Ks) by chromanols.
2000,
Pubmed
,
Xenbase
Mackie,
Vascular KCNQ potassium channels as novel targets for the control of mesenteric artery constriction by vasopressin, based on studies in single cells, pressurized arteries, and in vivo measurements of mesenteric vascular resistance.
2008,
Pubmed
Ng,
Expression and function of the K+ channel KCNQ genes in human arteries.
2011,
Pubmed
Ohya,
Molecular variants of KCNQ channels expressed in murine portal vein myocytes: a role in delayed rectifier current.
2003,
Pubmed
Salata,
A novel benzodiazepine that activates cardiac slow delayed rectifier K+ currents.
1998,
Pubmed
,
Xenbase
Sanguinetti,
Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.
1996,
Pubmed
,
Xenbase
Schenzer,
Molecular determinants of KCNQ (Kv7) K+ channel sensitivity to the anticonvulsant retigabine.
2005,
Pubmed
,
Xenbase
Schroeder,
A constitutively open potassium channel formed by KCNQ1 and KCNE3.
2000,
Pubmed
,
Xenbase
Seebohm,
Pharmacological activation of normal and arrhythmia-associated mutant KCNQ1 potassium channels.
2003,
Pubmed
,
Xenbase
Towart,
Blockade of the I(Ks) potassium channel: an overlooked cardiovascular liability in drug safety screening?
2009,
Pubmed
Wuttke,
The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate.
2005,
Pubmed
,
Xenbase
Yeung,
Electrophysiological and functional effects of the KCNQ channel blocker XE991 on murine portal vein smooth muscle cells.
2005,
Pubmed
Yeung,
Molecular expression and pharmacological identification of a role for K(v)7 channels in murine vascular reactivity.
2007,
Pubmed
Yeung,
Expression profile and characterisation of a truncated KCNQ5 splice variant.
2008,
Pubmed
,
Xenbase
Zhong,
Participation of KCNQ (Kv7) potassium channels in myogenic control of cerebral arterial diameter.
2010,
Pubmed
