THE RELATIONSHIP BETWEEN CONTRACTION AND INTRACELLULAR SODIUM IN RAT AND GUINEA-PIG VENTRICULAR MYOCYTES

1. The contraction, measured optically, and the intracellular Na+ activity (a(Na)i), measured with the Na+-sensitive fluorescent dye SBFI, have been recorded simultaneously in rat and guinea-pig ventricular myocytes. 2. In rat and guinea-pig ventricular myocytes at rest, a(Na)i was 7.8 +/- 0.3 mM (n = 4) and 5.1 +/- 0.3 mM (n = 16), respectively. 3. When both rat and guinea-pig ventricular myocytes were stimulated at 1 Hz after a rest there was usually a gradual increase in twitch shortening (referred to as a 'staircase') over several minutes accompanied by an increase in a(Na)i over a similar time course. Twitch shortening increased by 21 +/- 3% (n = 6) and 20 +/- 4% (n = 16) (of steady-state twitch shortening during 1 Hz stimulation) per millimolar rise in a(Na)i in rat and guinea-pig ventricular myocytes, respectively. 4. When rat and guinea-pig ventricular myocytes were exposed to strophanthidin to block the Na+-K+ pump, there were increases in twitch shortening and a(Na)i over similar time courses. Twitch shortening increased by 24 +/- 4% (n = 5) and 20 +/- 3% (n = 10) (of control twitch shortening) per millimolar rise in a(Na)i in rat and guinea-pig ventricular myocytes respectively. 5. The inotropic effect of cardiac glycosides, such as strophanthidin, is widely regarded to be principally the result of the rise in a(Na)i. The similarity of the relation between twitch shortening and a(Na)i during the staircase and on application of strophanthidin suggests that the progressive increase in the strength of contraction during the staircase was also linked to the rise in a(Na)i. 6. In guinea-pig, but not rat, ventricular myocytes there was hysteresis in the relation between twitch shortening and a(Na)i on application and wash-off of strophanthidin. This indicates that strophanthidin has another inotropic action in guinea-pig ventricular myocytes. 7. A computer model of excitation-contraction coupling has been developed to simulate the staircase and the action of cardiac glycoside and to account for the relation between contraction and intracellular Na+.