Expression and function of the K+ channel KCNQ genes in human arteries

Authors


Dr Iain A Greenwood, Biomedical Sciences, Ion Channels and Cell Signaling Research Centre, St. George's, University of London, Cranmer Terrace, London SW17 0RE, UK. E-mail: i.greenwood@sgul.ac.uk

Abstract

BACKGROUND AND PURPOSEKCNQ-encoded voltage-gated potassium channels (Kv7) have recently been identified as important anti-constrictor elements in rodent blood vessels but the role of these channels and the effects of their modulation in human arteries remain unknown. Here, we have assessed KCNQ gene expression and function in human arteries ex vivo.

EXPERIMENTAL APPROACH Fifty arteries (41 from visceral adipose tissue, 9 mesenteric arteries) were obtained from subjects undergoing elective surgery. Quantitative RT-PCR experiments using primers specific for all known KCNQ genes and immunohistochemsitry were used to show Kv7 channel expression. Wire myography and single cell electrophysiology assessed the function of these channels.

KEY RESULTSKCNQ4 was expressed in all arteries assessed, with variable contributions from KCNQ1, 3 and 5. KCNQ2 was not detected. Kv7 channel isoform-dependent staining was revealed in the smooth muscle layer. In functional studies, the Kv7 channel blockers, XE991 and linopirdine increased isometric tension and inhibited K+ currents. In contrast, the Kv7.1-specific blocker chromanol 293B did not affect vascular tone. Two Kv7 channel activators, retigabine and acrylamide S-1, relaxed preconstricted arteries, actions reversed by XE991. Kv7 channel activators also suppressed spontaneous contractile activity in seven arteries, reversible by XE991.

CONCLUSIONS AND IMPLICATIONS This is the first study to demonstrate not only the presence of KCNQ gene products in human arteries but also their contribution to vascular tone ex vivo.

LINKED ARTICLE This article is commented on by Mani and Byron, pp. 38–41 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.01065.x

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