Cerebrovascular responses in mice deficient in the potassium channel, TREK-1.
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 alpha-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. alpha-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 alpha-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.
Namiranian
Khodadad
K
Department of Anesthesiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Lloyd
Eric E
EE
Crossland
Randy F
RF
Marrelli
Sean P
SP
Taffet
George E
GE
Reddy
Anilkumar K
AK
Hartley
Craig J
CJ
Bryan
Robert M
RM
D000200:Action Potentials; D000818:Animals; D001011:Aorta / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010641:Phenotype; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024683:Potassium Channels, Tandem Pore Domain / Q000172:deficiency* / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D017962:alpha-Linolenic Acid / Q000378:metabolism
D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D024683:Potassium Channels, Tandem Pore Domain; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C103742:potassium channel protein TREK-1; D017962:alpha-Linolenic Acid; D016718:Arachidonic Acid; D009569:Nitric Oxide; D011451:Prostaglandin-Endoperoxide Synthases; D011188:Potassium