当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > Molecular expression and pharmacological identification of a role for K(v)7 channels in murine vascular reactivity.

Molecular expression and pharmacological identification of a role for K(v)7 channels in murine vascular reactivity.

Abstract：

BACKGROUND AND PURPOSE:This study represents a novel characterisation of KCNQ-encoded potassium channels in the vasculature using a variety of pharmacological and molecular tools to determine their role in contractility. EXPERIMENTAL APPROACH:Reverse transcriptase polymerase chain reaction (RT-PCR) experiments were undertaken on RNA isolated from mouse aorta, carotid artery, femoral artery and mesenteric artery using primers specific for all known KCNQ genes. RNA isolated from mouse heart and brain were used as positive controls. Pharmacological experiments were undertaken on segments from the same blood vessels to determine channel functionality. Immunocytochemical experiments were performed on isolated myocytes from thoracic aorta. KEY RESULTS:All blood vessels expressed KCNQ1, 4 and 5 with hitherto 'neuronal' KCNQ4 being, surprisingly, the most abundant. The correlated proteins K(v)7.1, K(v)7.4 and K(v)7.5 were identified in the cell membranes of aortic myocytes by immunocytochemistry. Application of three compounds known to activate K(v)7 channels, retigabine (2 -20 microM), flupirtine (20 microM) and meclofenamic acid (20 microM), relaxed vessels precontracted by phenylephrine or 1 mM 4-aminopyridine but had no effect on contractions produced by 60 mM KCl or the K(v)7 channel blocker XE991 (10 microM). All vessels tested contracted upon application of the K(v)7 channel blockers XE991 and linopirdine (0.1-10 microM). CONCLUSIONS AND IMPLICATIONS:Murine blood vessels exhibit a distinctive KCNQ expression profile with 'neuronal' KCNQ4 dominating. The ion channels encoded by KCNQ genes have a crucial role in defining vascular reactivity as K(v)7 channel blockers produced marked contractions whereas K(v)7 channel activators were effective vasorelaxants.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Yeung SY,Pucovský V,Moffatt JD,Saldanha L,Schwake M,Ohya S,Greenwood IA

doi

10.1038/sj.bjp.0707284

subject

Has Abstract

pub_date

2007-07-01 00:00:00

pages

758-70

issue

eissn

0007-1188

issn

1476-5381

pii

0707284

journal_volume

151

pub_type

杂志文章

在线工具

Molecular expression and pharmacological identification of a role for K(v)7 channels in murine vascular reactivity.