Cerebrovascular responses in mice deficient in the potassium channel, TREK-1

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

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

We tested the hypothesis that TREK-1, a two-pore domain K channel, is involved with dilations in arteries. Because there are no selective activators or inhibitors of TREK-1, we generated a mouse line deficient in TREK-1. Endothelium-mediated dilations were not different in arteries from wild-type (WT) and TREK-1 knockout (KO) mice. This includes dilations of the middle cerebral artery to ATP, dilations of the basilar artery to ACh, and relaxations of the aorta to carbachol, a cholinergic agonist. The nitric oxide (NO) and endothelium-dependent hyperpolarizing factor components of ATP dilations were identical in the middle cerebral arteries of WT and TREK-1 KO mice. Furthermore, the NO and cyclooxygenase-dependent components were identical in the basilar arteries of the different genotypes. Dilations of the basilar artery to α-linolenic acid, an activator of TREK-1, were not affected by the absence of TREK-1. Whole cell currents recorded using patch-clamp techniques were similar in cerebrovascular smooth muscle cells (CVSMCs) from WT and TREK-1 KO mice. α-linolenic acid or arachidonic acid increased whole cell currents in CVSMCs from both WT and TREK-1 KO mice. The selective blockers of large-conductance Ca-activated K channels, penitrem A and iberiotoxin, blocked the increased currents elicited by either α-linolenic or arachidonic acid. In summary, dilations were similar in arteries from WT and TREK-1 KO mice. There was no sign of TREK-1-like currents in CVSMCs from WT mice, and there were no major differences in currents between the genotypes. We conclude that regulation of arterial diameter is not altered in mice lacking TREK-1.

Original languageEnglish (US)
Pages (from-to)R461-R469
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume299
Issue number2
DOIs
StatePublished - Aug 2010

Keywords

  • Cerebrovascular circulation
  • KCNK2
  • Potassium channels
  • TREK-1 knockout
  • Two-pore domain potassium channels (K)
  • Vasodilation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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