Key result
KCNQ4 was expressed in all human arteries assessed, and Kv7 channel blockers increased isometric tension while Kv7 activators relaxed preconstricted arteries.
This study provides the first evidence that KCNQ gene products are present in human arteries and functionally contribute to regulating vascular tone.
May implicate Kv7 channels in human vascular tone; leaves open therapeutic targeting pending clinical studies.
BACKGROUND AND PURPOSE: KCNQ-encoded voltage-gated potassium channels (K(v) 7) 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 K(v) 7 channel expression. Wire myography and single cell electrophysiology assessed the function of these channels. KEY RESULTS: KCNQ4 was expressed in all arteries assessed, with variable contributions from KCNQ1, 3 and 5. KCNQ2 was not detected. K(v) 7 channel isoform-dependent staining was revealed in the smooth muscle layer. In functional studies, the K(v) 7 channel blockers, XE991 and linopirdine increased isometric tension and inhibited K(+) currents. In contrast, the K(v) 7.1-specific blocker chromanol 293B did not affect vascular tone. Two K(v) 7 channel activators, retigabine and acrylamide S-1, relaxed preconstricted arteries, actions reversed by XE991. K(v) 7 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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Ng et al. (2010) studied Patients undergoing elective surgery (n=50). Kv7 channel modulators (XE991, linopirdine, retigabine, acrylamide S-1) vs. Vehicle or baseline was evaluated on KCNQ gene expression and changes in isometric tension. KCNQ4 was expressed in all human arteries assessed, and Kv7 channel blockers increased isometric tension while Kv7 activators relaxed preconstricted arteries.
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