Effect of quinidine and temperature on sodium uptake and contraction frequency of cultured rat myocardial cells

The effects of quinidine and temperature on Na influx and contraction frequency of synchronously contracting rat myocardial cells in monolayer cultures were studied. Quinidine (10^-6 M to 10^-2 M) produced a prompt reduction in Na influx, maximum after 30 seconds of exposure, and dose dependent along a sigmoid log dose response curve. At 37°C, Na influx (μmol/10¹¹ cells per sec) decreased from 30.19 to 24.70 (P < 0.001) and 10.49 (P < 0.001) on exposure to quinidine, 10^-6 and 10^-2 M, respectively. Simultaneously the contraction frequency decreased from a control of 120/min to 105/min and 48/min with 10^-6 M and 5 x 10^-4 M quinidine. At higher concentrations spontaneous contractions ceased. The effects on Na influx and contraction were reversible by washing the cells free of the drug (30 seconds). A temperature dependent decrease in the Na influx between 37°C and 22°C also induced a decrease in contraction frequency. Between 25°C and 35°C the Q₁₀ values for Na influx and contraction frequency were 2.41 and 2.44 respectively. Under all conditions tested there was a constant linear relationship (r = 0.98) between Na influx and contraction frequency for all values of Na influx greater than 11.82 μmol/10¹¹ cells per sec. Na influx and contraction frequency were insensitive to tetrodotoxin (10^-5 g/ml) but very sensitive to verapamil and to changes in extracellular Na. Quinidine affected only the verapamil sensitive Na influx. The results indicate a close relationship between verapamil sensitive inward Na movement and automaticity in these cells and demonstrate that the quinidine induced changes in automaticity are closely linked to the effect on Na influx.