Disruption of K2P6.1 produces vascular dysfunction and hypertension in mice

Eric E. Lloyd, Randy F. Crossland, Sharon C. Phillips, Sean P. Marrelli, Anilkumar K. Reddy, George Taffet, Craig J. Hartley, Robert M. Bryan

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

K2P6.1, a member of the 2-pore domain K channel family, is highly expressed in the vascular system; however, its function is unknown. We tested the following hypotheses. K2P6.1 regulates the following: (1) systemic blood pressure; (2) the contractile state of arteries; (3) vascular smooth muscle cell migration; (4) proliferation; and/or (5) volume regulation. Mice lacking K2P6.1 (KO) were generated by deleting exon 1 of Kcnk6. Mean arterial blood pressure in both anesthetized and awake KO mice was increased by 17±2 and 26±3 mm Hg, respectively (P<0.05). The resting membrane potential in freshly dispersed vascular smooth muscle cells was depolarized by 17±2 mV in the KO compared with wild-type littermates (P<0.05). The contractile responses to KCl (P<0.05) and BAY K 8644 (P<0.01), an activator of L-type calcium channels, were enhanced in isolated segments of aorta from KO mice. However, there was no difference in the current density of L-type calcium channels. Responses to U46619, an agent that activates rho kinase, showed an enhanced contraction in aorta from KO mice (P<0.001). The BAY K 8644-mediated increase in contraction was decreased to wild-type levels when treated with Y27632, a rho kinase inhibitor, (P<0.05). K 2P6.1 does not appear to be involved with migration, proliferation, or volume regulation in cultured vascular smooth muscle cells. We conclude that K2P6.1 deficiency induces vascular dysfunction and hypertension through a mechanism that may involve smooth muscle cell depolarization and enhanced rho kinase activity.

Original languageEnglish (US)
Pages (from-to)672-678
Number of pages7
JournalHypertension
Volume58
Issue number4
DOIs
StatePublished - Oct 2011

Keywords

  • 2-pore domain potassium channels (K)
  • hypertension
  • K6.1
  • Kcnk6
  • resting membrane potential
  • Rho kinase
  • TWIK-2

ASJC Scopus subject areas

  • Internal Medicine

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