ELECTROPHYSIOLOGICAL EFFECTS OF THE SALICYLATES ON ISOLATED ATRIAL MUSCLE OF THE RABBIT

Abstract

1 Intracellular recordings were made from cells of the sinoatrial (S-A) node region and from atrial muscle fibres of rabbit hearts. The effects of sodium salicylate and 5-bromo salicylate on various parameters of the membrane action potential were studied.2 5-Bromo salicylate (30-100 muM) and sodium salicylate (300-500 muM) caused a dose-dependent decrease in the frequency of discharge of the SA node cells. Applications of atropine (2.6 muM) with propranolol (3.3 muM) did not affect the negative chronotropic effect, whereas adrenaline (5 muM) reversed it.3 Depolarization and shortening of the action potential duration were found in atrial muscle fibres after the application of 5-bromo salicylate (60-100 muM). The reduction of the action potential duration (APD) was not affected by atropine (2.6 muM).4 Higher concentrations of 5-bromo salicylate (> 100 muM) also caused a dose-dependent reduction in the action potential amplitude (APA), in the overshoot (OS) of the action potential and in the maximum rate of rise of the action potential (V(max)). All these effects were completely reversed on washing.5 Substitution of the NaCl of the bathing Tyrode solution by an equimolar concentration of Na isethionate did not affect the plateau depression induced by the salicylates in atrial muscle fibres.6 After increasing the K concentration to 27 mM in the presence of isoprenaline (1 muM), ;slow responses' were obtained upon stimulation. 5-Bromo salicylate (20-60 muM) and sodium salicylate (100 muM) decreased reversibly the amplitude and the rate of rise of the ;slow response'.7 A four fold increase in Ca concentration of the standard Tyrode solution did not antagonize the plateau depression of atrial muscle fibres or the negative chronotropism induced by salicylates.8 Addition of CsCl (10 mM) to the Tyrode solution did not affect the shortening of the APD induced by the salicylates in atrial muscle fibres.9 When the K concentration in the Tyrode solution was increased from 2.7 mM to 5.4 mM, the effects of 5-bromo salicylate on the APA, OS and V(max) were potentiated. However, a significant reduction in the shortening of the APD produced by the salicylate was observed.10 It is suggested that the salicylates possibly depress the slow inward current in both S-A node cells and atrial muscle fibres of the rabbit heart. In atrial muscle fibres, a concomitant increase in the outward potassium current is probably involved.