Mechanisms behind the biphasic contractile response to potassium depolarization in isolated rat cerebral arteries

ED Hogestatt and KE Andersson

Ring segments of rat basilar and middle cerebral arteries were suspended in a small volume muscle bath and the mechanical activity recorded "isometrically." K+ excess (124 mM) evoked a biphasic contractile response, composed of an early rapid phase (phase A) and an ensuing slow phase (phase B), separated by a small transient relaxation. Cooling produced a gradual dissociation of the two contraction components and depressed their maxima. Readdition of Ca++ to arteries previously depolarized by K+ in the absence of external Ca++ also elicited a biphasic contraction, which excludes the possibility that the initial transient response was initiated by a burst of spikes. Ca++ removal considerably suppressed and 1 mM La abolished both components of the K+ contraction. Prolonged treatment (greater than 3 hr) in Ca++-free, ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid (1 mM)-containing medium reduced neither the amplitude of phase A nor that of phase B of the contraction induced by the simultaneous addition of K+ and Ca++. This indicates that the early rapid component was not due to a release of intracellularly stored Ca++. Nifedipine preferentially inhibited phase B of the K+ contraction. The drug also effectively suppressed Ca++-induced contractions in arteries previously depolarized by K+ in Ca++-free medium. The inhibition produced by nifedipine consisted of a reduction of both the maximum and the slope of the concentration-response curve for Ca++. The results of the present study indicate that K+ initiates contraction in rat cerebral arteries by promoting the movement of extracellular and/or superficially bound Ca++ to the cytoplasmic matrix.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 228, Issue 1, pp. 187-195, 01/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics