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

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Abstract
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(-1) 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 degrees C, Na influx (mumol/10(11) cells per sec) decreased from 30.19 to 24.70 (P less than 0.001) and 10.49 (P less than 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 degrees C and 22 degrees C also induced a decrease in contraction frequency. Between 25 degrees C and 35 degrees 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 mumol/10(11) 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.