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

1. 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. 2. 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. 3. 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. 4. 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. 5. These actions took place over patho-physiological ranges of [K+]o and [Mg2+]o. 6. Maintenance of a constant [K+]o/[Mg2+]o ratio, irrespective of the exact [K+]o and [Mg2+]o, produced similar degrees of maximum tension. 7. Use of intact vascular ring preparations and helically-cut vascular strips produced similar results with varying [K+]o/[Mg2+]o. 8. 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. 9. 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.