Hypercapnic acidosis activates KATP channels in vascular smooth muscles.
ATP-sensitive K+ channels (KATP) couple intermediary metabolism to cellular activity, and may play a role in the autoregulation of vascular tones. Such a regulation requires cellular mechanisms for sensing O2, CO2, and pH. Our recent studies have shown that the pancreatic KATP isoform (Kir6.2/SUR1) is regulated by CO2/pH. To identify the vascular KATP isoform(s) and elucidate its response to hypercapnic acidosis, we performed these studies on vascular smooth myocytes (VSMs). Whole-cell and single-channel currents were studied on VSMs acutely dissociated from mesenteric arteries and HEK293 cells expressing Kir6.1/SUR2B. Hypercapnic acidosis activated an inward rectifier current that was K+-selective and sensitive to levcromakalim and glibenclamide with unitary conductance of approximately 35pS. The maximal activation occurred at pH 6.5 to 6.8, and the current was inhibited at pH 6.2 to 5.9. The cloned Kir6.1/SUR2B channel responded to hypercapnia and intracellular acidification in an almost identical pattern to the VSM current. In situ hybridization histochemistry revealed expression of Kir6.1/SUR2B mRNAs in mesenteric arteries. Hypercapnia produced vasodilation of the isolated and perfused mesenteric arteries. Pharmacological interference of the KATP channels greatly eliminated the hypercapnic vasodilation. These results thus indicate that the Kir6.1/SUR2B channel is a critical player in the regulation of vascular tones during hypercapnic acidosis.
Department of Biology, Georgia State University, 24 Peachtree Center Ave, Atlanta, Ga 30302-4010, USA.
Xueren
X
Wang
Jianping
J
Wu
Li
L
Li
Fuxue
F
Chen
Runping
R
Wang
Chun
C
Jiang
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D046508:Culture Techniques; D004553:Electric Conductivity; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000503:physiopathology; D008638:Mesenteric Arteries / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000378:metabolism; D064233:Sulfonylurea Receptors; D014664:Vasodilation
C577507:ABCC8 protein, human; D018528:ATP-Binding Cassette Transporters; C577509:Abcc8 protein, rat; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate