Importance of magnesium and potassium concentration on basal tone and 5‐HT‐induced contractions in canine isolated coronary artery

Abstract

In vitro studies were undertaken to investigate the effects of external potassium ([K+]o) and magnesium ([Mg2+]o) concentration on canine coronary arterial basal tone and on 5‐hydroxytryptamine (5‐HT)‐induced contractions. Acute withdrawal of, or reduction in, [K+]o produced relaxation of basal tone in isolated coronary arteries, whereas acute withdrawal (but not reduction) of [Mg2+]o produced contraction of these blood vessels. The magnitude of coronary contraction obtained on withdrawal of [Mg2+]o was dependent upon the [K+]o; the higher the [K+]o, the greater the contraction. The precise ratio of [K+]o/[Mg2+]o appeared to be important in dictating the degree of contraction (maximum response) and sensitivity (EC50) of canine coronary vascular smooth muscle cells to 5‐HT. The EC50 to 5‐HT was enhanced by increases in the [K+]o/[Mg2+]o ratio, whereas the ability of 5‐HT to induce a maximal contraction was attenuated by decreases in the [K+]o; the latter being modulated by [Mg2+]o. Small changes in [Mg2+]o could effect large changes in the EC50 as [K+]o was lowered. These actions took place over patho‐physiological 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. Use of intact vascular 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 [K+]o/[Mg2+]o ratios. These results suggest: (1) that basal tone and contractility of canine coronary vascular smooth muscle cells appear to be exquisitely sensitive to alterations in extracellular K+ and Mg2+; and (2) 5‐HT receptor‐operated Ca2+ channels, as well as those Ca2+ channels involved in generation of coronary arterial basal tone are modulated and controlled by the precise concentrations of [K+]o and [Mg2+]o. 1988 British Pharmacological Society