Role of potassium channels in relaxations of isolated canine basilar arteries to acidosis.
OBJECTIVE
Concentration of hydrogen ions is an important regulator of cerebral arterial tone under physiological and pathological conditions. Previous studies demonstrated that in cerebral arteries, relaxations to hypercapnia are due to decrease in extracellular pH. The present study was designed to determine the role of potassium channels in mediation of cerebral arterial relaxations induced by extracellular acidosis.


METHODS
Rings of canine basilar arteries without endothelium were suspended for isometric force recording. Acidosis (pH 7.3 to 7.0) was produced by incremental addition of hydrochloric acid (1.0N). The concentration of hydrogen ions was continuously monitored with a pH meter.


RESULTS
During contractions to UTP, acidosis (pH 7.3 to 7.0) induced pH-dependent relaxations. These relaxations were abolished in arteries contracted by potassium chloride (20 mmol/L). A nonselective potassium channel inhibitor, BaCl2 (10(-4) and 10(-4) mol/L), and an ATP-sensitive potassium channel inhibitor, glyburide (5 x 10(-6) mol/L), significantly reduced relaxations to acidosis. Furthermore, BaCl2 (10(-4) mol/L) and glyburide (5 x 10(-6) mol/L) abolished relaxations to an ATP-sensitive potassium channel opener, cromakalim (10(-8) to 3 x 10(-5) mol/L). However, these potassium channel inhibitors did not affect relaxations to a voltage-dependent calcium channel inhibitor, diltiazem (10(-8) to 10(-4) mol/L), and glyburide (5 x 10(-6) mol/L) did not alter relaxations to a nitric oxide donor, SIN-1 (10(-9) to 10(-4) mol/L). A calcium-activated potassium channel inhibitor, charybdotoxin (10(-7) mol/L), and a delayed rectifier potassium channel inhibitor, 4-aminopyridine (10(-3) mol/L), did not affect relaxations to acidosis.


CONCLUSIONS
These results suggest that extracellular acidosis causes relaxations of cerebral arteries in part by activation of potassium channels. ATP-sensitive potassium channels appear to contribute to acidosis-induced decrease in cerebral arterial tone.
Kinoshita
H
H
Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA.
Katusic
Z S
ZS
D015761:4-Aminopyridine / Q000494:pharmacology; D018528:ATP-Binding Cassette Transporters; D000138:Acidosis / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D001488:Basilar Artery / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects; D054086:KATP Channels; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D014544:Uridine Triphosphate / Q000494:pharmacology; D014664:Vasodilation
D018528:ATP-Binding Cassette Transporters; D017609:Barium Compounds; D002121:Calcium Channel Blockers; D002712:Chlorides; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; C024986:barium chloride; D018999:Charybdotoxin; C002385:linsidomine; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D008981:Molsidomine; D005905:Glyburide; D014544:Uridine Triphosphate