The action of promazine and thioridazine in isolated rat atria. 3. effects of varying concentrations of calcium and different frequencies and strengths of stimulation on contractile force and excitability

Abstract

The effects of promazine and thioridazine on electrically stimulated left rat atria were studied in the presence of varying concentrations of calcium and at different frequencies and strengths of stimulation. An increase of the calcium concentration, [Ca 2+] O, in the Ringer solution increased the force of contraction of the preparations. A slight decrease in excitability was found at [Ca 2+] O above 4.0 meq/1. Suprathreshold stimulation (50 mA) produced a considerable increase in contractile force when [Ca 2+] O was 2.0 meq/1, but on increasing the calcium concentration, this augmentation declined rapidly. On the basis of experiments with an adrenergic β-blocker, practolol, and atropine sulphate, it is concluded that suprathreshold stimulation releases noradrenaline as well as acetylcholine. The decrease in contractile force caused by promazine, 2.5 × 10 −5 M, and thioridazine, 2.5 × 10 −5 M, was, to a certain extent, antagonized by increasing the concentration of Ca 2+. In atria stimulated at suprathreshold values, the results indicate that some sort of competition between Ca 2+ and the phenothiazine derivatives may exist, and it is assumed that the drugs interfere with the exchangeability of calcium available for contraction. The decrease in excitability caused by promazine, 2.5 × 10 −5 M, seemed to be independent of varying [Ca 2+ O. An increase in the frequency of contractions increased the threshold for electrical stimulation and reduced the contractile force (‘negative staircase’). Promazine, 2.5 × 10 −5 M, enhanced these effects. It is concluded that the degree of the phenothiazine-induced reduction in contractile force of isolated rat atria depends upon the calcium concentration of the Ringer solution and also on the frequency and strength of stimulation.