Role of inwardly rectifying K(+) channels in K(+)-induced cerebral vasodilatation in vivo.
We tested whether activation of inwardly rectifying K(+) (Kir) channels, Na(+)-K(+)-ATPase, or nitric oxide synthase (NOS) play a role in K(+)-induced dilatation of the rat basilar artery in vivo. When cerebrospinal fluid [K(+)] was elevated from 3 to 5, 10, 15, 20, and 30 mM, a reproducible concentration-dependent vasodilator response was elicited (change in diameter = 9 +/- 1, 27 +/- 4, 35 +/- 4, 43 +/- 12, and 47 +/- 16%, respectively). Responses to K(+) were inhibited by approximately 50% by the Kir channel inhibitor BaCl(2) (30 and 100 microM). In contrast, neither ouabain (1-100 microM, a Na(+)-K(+)-ATPase inhibitor) nor N(G)-nitro-L-arginine (30 microM, a NOS inhibitor) had any effect on K(+)-induced vasodilatation. These concentrations of K(+) also hyperpolarized smooth muscle in isolated segments of basilar artery, and these hyperpolarizations were virtually abolished by 30 microM BaCl(2). RT-PCR experiments confirmed the presence of mRNA for Kir2.1 in the basilar artery. Thus K(+)-induced dilatation of the basilar artery in vivo appears to partly involve hyperpolarization mediated by Kir channel activity and possibly another mechanism that does not involve hyperpolarization, activation of Na(+)-K(+)-ATPase, or NOS.
Chrissobolis
S
S
Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Ziogas
J
J
Chu
Y
Y
Faraci
F M
FM
Sobey
C G
CG
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002712:Chlorides / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010847:Picolines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011714:Pyrans / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D017609:Barium Compounds; D002712:Chlorides; D004791:Enzyme Inhibitors; D010847:Picolines; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011714:Pyrans; D012333:RNA, Messenger; D014665:Vasodilator Agents; D019806:Cromakalim; C024986:barium chloride; D009599:Nitroprusside; D019335:Nitroarginine; C061043:aprikalim; D010042:Ouabain; D019001:Nitric Oxide Synthase; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine; D011188:Potassium