Extracellular magnesium and potassium concentrations interact to modulate tone and reactivity of isolated canine cerebral vascular muscle.
In vitro studies were undertaken to investigate the effects of external potassium [K+]o, 0-7.1 mM, and magnesium [Mg2+]o, 0-4.8 mM, concentration on canine middle cerebral and basilar arterial basal tone and on 5-hydroxytryptamine (5-HT)-induced contractions. The lower the [K+]o, the greater the degree of spontaneous contraction upon acute withdrawal of [Mg2+]o. An inverse linear relationship between the concentration of [K+]o and the degree of cerebrovasospasm upon acute withdrawal of [Mg2+]o was observed over the range of 1-6 mM [K+]o. As [K+]o was increased, stepwise, the slow phase of the contractions became attenuated, while the magnitude of the fast phase became progressively smaller. Acute withdrawal of [K+]o produced contraction of middle cerebral and basilar arteries which could be modulated by the concentration of [Mg2+]o. The higher the [Mg2+]o, the less the tension developed upon acute withdrawal of [K+]o. Contractility to 5-HT was depressed when [K+]o was lowered. This attenuation was reversed completely when [Mg2+]o was acutely withdrawn. Sensitivity (EC50) of canine middle cerebral and basilar arteries to 5-HT was inversely related to the [K+]o/[Mg2+]o ratio. These actions took place over pathophysiological ranges of [K+]o and [Mg2+]o. Maintenance of a constant [K+]o/[Mg2+]o ratio, irrespective of the exact [K+]o and [Mg2+]o, produced similar degrees of maximum tension and sensitivity (EC50) to 5-HT. Use of intact ring preparations and helically cut vascular strips produced similar results with varying [K+]o/[Mg2+]o. A variety of pharmacological receptor antagonists (phentolamine, propranolol, atropine, diphenhydramine, cimetidine), as well as a prostaglandin cyclo-oxygenase inhibitor, did not modify the altered contractile responses or basal tone evoked by varying the [K+]o/[Mg2+]o ratios. These experiments suggest: (1) that basal tone and contractility of canine cerebral vascular smooth muscle cells appear to be exquisitely sensitive to alterations in extracellular K+ and Mg2+ and (2) that 5-HT receptor-operated Ca2+ channels, as well as those Ca2+ channels involved in the generation of cerebral arterial basal tone, are modulated and controlled by the precise concentrations of [K+]o and [Mg2+]o.
Murakawa
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Department of Physiology, State University of New York, Brooklyn.
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D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008274:Magnesium / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009129:Muscle Tonus / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology*; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology
D012701:Serotonin; D008274:Magnesium; D011188:Potassium