Effect of acidosis on tension and [Ca2+]i in rat cerebral arteries: is there a role for membrane potential?
The cellular mechanism responsible for the reduction of tension in cerebral small arteries to acidosis is not known. In this study the role of smooth muscle intracellular Ca2+ concentration ([Ca2+]i) and membrane potential for the relaxation to acidosis was investigated in isolated rat cerebral small arteries. Isometric force was measured simultaneously with [Ca2+]i (fura 2) or with membrane potential (intracellular microelectrodes), and acidosis was induced by increasing PCO2 or reducing HCO3- of the bathing solution. Both hypercapnic and normocapnic acidosis were associated with a reduction of intracellular pH [measured with 2',7'-bis-(carboxyethyl)-5 (and -6)-carboxyfluorescein], caused relaxation, and reduced [Ca2+]i. However, whereas hypercapnic acidosis caused hyperpolarization, normocapnic acidosis was associated with depolarization. It is concluded that a reduction of [Ca2+]i is in part responsible for the direct effect of the acidosis on the vascular smooth muscle both during normo- and hypercapnia. The mechanism responsible for the reduction of [Ca2+]i differs between the hypercapnic and normocapnic acidosis, being partly explained by hyperpolarization during hypercapnic acidosis, whereas it is seen despite depolarization during normocapnic acidosis.
Peng
H L
HL
Department of Pharmacology, University of Aarhus, Denmark.
Jensen
P E
PE
Nilsson
H
H
Aalkjaer
C
C
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002245:Carbon Dioxide / Q000494:pharmacology; D002536:Cerebral Arteries / Q000503:physiopathology*; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
D001639:Bicarbonates; D005452:Fluoresceins; D005456:Fluorescent Dyes; D002245:Carbon Dioxide; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D002118:Calcium