Disruption of K(2P)6.1 produces vascular dysfunction and hypertension in mice

Hypertension. 2011 Oct;58(4):672-8. doi: 10.1161/HYPERTENSIONAHA.111.175349. Epub 2011 Aug 29.


K(2P)6.1, 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. K(2P)6.1 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 K(2P)6.1 (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(2P)6.1 does not appear to be involved with migration, proliferation, or volume regulation in cultured vascular smooth muscle cells. We conclude that K(2P)6.1 deficiency induces vascular dysfunction and hypertension through a mechanism that may involve smooth muscle cell depolarization and enhanced rho kinase activity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Aorta / drug effects
  • Aorta / physiopathology*
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Calcium Channel Agonists / pharmacology
  • Disease Models, Animal
  • Hypertension / etiology*
  • Hypertension / physiopathology*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Mice, Knockout
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiopathology*
  • Potassium Channels, Tandem Pore Domain / deficiency
  • Potassium Channels, Tandem Pore Domain / genetics
  • Potassium Channels, Tandem Pore Domain / physiology*
  • Potassium Chloride / pharmacology
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology
  • Vasoconstrictor Agents / pharmacology
  • rho-Associated Kinases / physiology


  • Calcium Channel Agonists
  • Potassium Channels, Tandem Pore Domain
  • Vasoconstrictor Agents
  • Potassium Chloride
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • rho-Associated Kinases