Do KV 7.1 channels contribute to control of arterial vascular tone?

KV 7.1 voltage-gated potassium channels are expressed in vascular smooth muscle cells (VSMC) of diverse arteries, including mesenteric arteries. Based on pharmacological evidence using R-L3 (KV 7.1 channel opener), HMR1556, chromanol 293B (KV 7.1 channel blockers), stimulation of these channels has been suggested to evoke profound relaxation in various vascular beds of rats. However, the specificity of these drugs in vivo is uncertain. We used Kcnq1-/- mice and pharmacological tools to determine whether KV 7.1 channels play a role in the regulation of arterial tone. R-L3 produced similar concentration-dependent relaxations (EC50  ~ 1.4 μM) of arteries from wild-type (Kcnq1+/+ ) and Kcnq1-/- mice, pre-contracted with either phenylephrine or 60 mM KCl. This relaxation was not affected by 10 μM chromanol 293B, 10 μM HMR1556 or 30 μM XE991 (pan-KV 7 channel blocker). The anti-contractile effects of the perivascular adipose tissue (PVAT) were normal in Kcnq1-/- arteries. Chromanol 293B and HMR1556 did not affect the anti-contractile effects of (PVAT). Isolated VSMCs from Kcnq1-/- mice exhibited normal peak KV currents. The KV 7.2-5 channel opener retigabine caused similar relaxations in Kcnq1-/- and wild-type vessels. We conclude that KV 7.1 channels were apparently not involved in the control of arterial tone by α1 -adrenoceptor agonists and PVAT. In addition, R-L3 is an inappropriate pharmacological tool for studying the function of native vascular KV 7.1 channels in mice. © 2016 The British Pharmacological Society.

Citation

Dmitry Tsvetkov, Mario Kaßmann, Jean-Yves Tano, Lan Chen, Johanna Schleifenbaum, Jakob Voelkl, Florian Lang, Yu Huang, Maik Gollasch. Do KV 7.1 channels contribute to control of arterial vascular tone? British journal of pharmacology. 2017 Jan;174(2):150-162

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PMID: 28000293

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