Pharmacological dissection of Kv7.1 channels in systemic and pulmonary arteries

Chadha PS, Zunke F, Davis AJ, Jepps TA, Linders JTM, Schwake M, Towart R, Greenwood IA (2012)
British Journal of Pharmacology 166(4): 1377-1387.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Chadha, Preet S.; Zunke, Friederike; Davis, Alison J.; Jepps, Thomas A.; Linders, Joannes T. M.; Schwake, MichaelUniBi ; Towart, Rob; Greenwood, Iain A.
Alternativer Titel
KV7.1 channels in the vasculature
Abstract / Bemerkung
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 µM) and JNJ39490282 (JNJ282; 1 µM) had no contractile effects in arteries, whereas the pan-Kv7 channel blocker linopirdine (10 µM) 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.
Erscheinungsjahr
2012
Zeitschriftentitel
British Journal of Pharmacology
Band
166
Ausgabe
4
Seite(n)
1377-1387
ISSN
0007-1188
Page URI
https://pub.uni-bielefeld.de/record/2953342

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Chadha PS, Zunke F, Davis AJ, et al. Pharmacological dissection of Kv7.1 channels in systemic and pulmonary arteries. British Journal of Pharmacology. 2012;166(4):1377-1387.
Chadha, P. S., Zunke, F., Davis, A. J., Jepps, T. A., Linders, J. T. M., Schwake, M., Towart, R., et al. (2012). Pharmacological dissection of Kv7.1 channels in systemic and pulmonary arteries. British Journal of Pharmacology, 166(4), 1377-1387. https://doi.org/10.1111/j.1476-5381.2012.01863.x
Chadha, P. S., Zunke, F., Davis, A. J., Jepps, T. A., Linders, J. T. M., Schwake, M., Towart, R., and Greenwood, I. A. (2012). Pharmacological dissection of Kv7.1 channels in systemic and pulmonary arteries. British Journal of Pharmacology 166, 1377-1387.
Chadha, P.S., et al., 2012. Pharmacological dissection of Kv7.1 channels in systemic and pulmonary arteries. British Journal of Pharmacology, 166(4), p 1377-1387.
P.S. Chadha, et al., “Pharmacological dissection of Kv7.1 channels in systemic and pulmonary arteries”, British Journal of Pharmacology, vol. 166, 2012, pp. 1377-1387.
Chadha, P.S., Zunke, F., Davis, A.J., Jepps, T.A., Linders, J.T.M., Schwake, M., Towart, R., Greenwood, I.A.: Pharmacological dissection of Kv7.1 channels in systemic and pulmonary arteries. British Journal of Pharmacology. 166, 1377-1387 (2012).
Chadha, Preet S., Zunke, Friederike, Davis, Alison J., Jepps, Thomas A., Linders, Joannes T. M., Schwake, Michael, Towart, Rob, and Greenwood, Iain A. “Pharmacological dissection of Kv7.1 channels in systemic and pulmonary arteries”. British Journal of Pharmacology 166.4 (2012): 1377-1387.
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