期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 166, 期 4, 页码 1377-1387出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1476-5381.2012.01863.x
关键词
voltage-dependent K plus channel; KCNQ; Kv7; vascular smooth muscle; arterial tone
资金
- British Heart Foundation [PG/09/104, PG\07\127\24235]
- BBSRC-CASE [BB/G016321/1]
- NeuroSearch A/S
- Deutsche Forschungsgemeinschaft [SCHW866/4-1, SFB877]
- BBSRC [BB/G016321/1] Funding Source: UKRI
BACKGROUND AND PURPOSE The aim of this study was to characterize the functional impact of KCNQ1-encoded voltage-dependent potassium channels (Kv7.1) in the vasculature. EXPERIMENTAL APPROACH Mesenteric arteries, intrapulmonary arteries and thoracic aortae were isolated from adult rats. Kv7.1 channel expression was established by fluorescence immunocytochemistry. Wire myography determined functionality of these channels in response to selective blockers and activators. Xenopus oocytes expressing Kv7.1 channels were used to assess the effectiveness of selective Kv7.1 channel blockers. KEY RESULTS Kv7.1 channels were identified in arterial myocytes by immunocytochemistry. Kv7.1 blockers HMR1556, L-768,673 (10 mu M) and JNJ39490282 (JNJ282; 1 mu M) had no contractile effects in arteries, whereas the pan-Kv7 channel blocker linopirdine (10 mu M) evoked robust contractions. Application of two compounds purported to activate Kv7.1 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, Kv7.1 channels expressed in arterial myocytes are functional ion channels. Although these channels do not appear to contribute to resting vascular tone, Kv7.1 activators were effective vasorelaxants.
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