TWIK-related two-pore domain potassium channel TREK-1 in carotid endothelium of normotensive and hypertensive mice.
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.
Pokojski
Sebastian
S
Department of Internal Medicine-Nephrology, Philipps-University, Baldingerstrasse, 35033 Marburg, Hessen, Germany.
Busch
Christoph
C
Grgic
Ivica
I
Kacik
Michael
M
Salman
Waleed
W
Preisig-Müller
Regina
R
Heyken
Willm-Thomas
WT
Daut
Jürgen
J
Hoyer
Joachim
J
Köhler
Ralf
R
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
C486372:Kcnk1 protein, mouse; C487530:Kcnk1 protein, rat; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1