title: TWIK-related two-pore domain potassium channel TREK-1 in carotid endothelium of normotensive and hypertensive mice.
abstract: OBJECTIVE
  Potassium channels are essential elements of endothelial function. Recently, evidence emerged that the TWIK (tandem of P domains in a weak inwardly rectifying K+ channel)-related K+ channel (TREK-1) of the two-pore domain potassium channel gene family (K2P) may be involved in the regulation of vascular tone. However, the functional and molecular characterization of vascular TREK-1 is incomplete. In this study, we therefore analysed the functional expression of TREK-1 in the endothelium. Moreover, we hypothesized that changes in channel expression may contribute to altered endothelial vasodilator response under conditions of elevated blood pressure.
  
  
  RESULTS
  Gene expression and function of endothelial TREK-1 were analysed by single-cell RT-PCR, the patch-clamp technique and pressure myography in murine carotid arteries (CA). K+ outward currents displaying the characteristics of TREK-1 were observed following various TREK-1-activating stimuli such as membrane stretch, intracellular acidosis, polyunsaturated fatty acids, isoflurane (ISOFL), riluzole, and acetylcholine (ACh). In K(Ca)3.1(-/-) mice exhibiting elevated blood pressure, endothelial TREK-1 currents and TREK-1 mRNA expression were enhanced as compared with normotensive control mice. TREK-1-mediated vasodilator responses to alpha-linolenic acid, ISOFL, or ACh were increased. A similar up-regulation of endothelial TREK-1 was observed in spontaneously hypertensive rats.
  
  
  CONCLUSIONS
  We have found that TREK-1 is an endothelial K+ channel capable of producing hyperpolarization and vasodilation. A correlation between hypertension and up-regulation of TREK-1 was observed in two different animal models of elevated blood pressure. Thus, TREK-1 may play a protective role in the cardiovascular system by providing a novel type of endothelial hyperpolarization-mediated vasodilator response.
authors.affiliation: Department of Internal Medicine-Nephrology, Philipps-University, Baldingerstrasse, 35033 Marburg, Hessen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Pokojski
authors.forename: Christoph
authors.initials: C
authors.lastname: Busch
authors.forename: Ivica
authors.initials: I
authors.lastname: Grgic
authors.forename: Michael
authors.initials: M
authors.lastname: Kacik
authors.forename: Waleed
authors.initials: W
authors.lastname: Salman
authors.forename: Regina
authors.initials: R
authors.lastname: Preisig-Müller
authors.forename: Willm-Thomas
authors.initials: WT
authors.lastname: Heyken
authors.forename: Jürgen
authors.initials: J
authors.lastname: Daut
authors.forename: Joachim
authors.initials: J
authors.lastname: Hoyer
authors.forename: Ralf
authors.initials: R
authors.lastname: Köhler
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002339:Carotid Arteries / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015854:Up-Regulation / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: C486372:Kcnk1 protein, mouse; C487530:Kcnk1 protein, rat; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1