Effects of caffeine on intracellular sodium activity in cardiac Purkinje fibres: relation to force.

1. An increase in cytoplasmic calcium by caffeine would lead to Ca extrusion via the Na/Ca exchange. The hypotheses were investigated that, as a consequence, caffeine might increase intracellular sodium activity (aiNa) and that the relation between aiNa and force might be conditioned by the Ca load. 2. Action potential, aiNa and contractile force were recorded in sheep Purkinje fibres during exposure to caffeine under conditions that decrease or increase the Ca load by different mechanisms. 3. In Tyrode solution, caffeine (8 mM) increased aiNa from 8.05 +/- 0.20 to 10.52 +/- 0.40 mM (+30.5%) and had a triphasic effect on force: an initial transient increase (+93.6%), a subsequent decrease (-37.1%) (negative inotropy) and slow partial recovery (+8.9%). 4. Decreasing the Ca load by means of manganese (1 mM) decreased aiNa and force. Adding caffeine re-increased aiNa and no longer caused a negative inotropic action. Cadmium (0.2 mM) also decreased aiNa, and caffeine reincreased it although far less than in Tyrode solution. 5. High [K]o (10 mM) and tetrodotoxin (5 microM) decreased aiNa as well as force. In their presence, caffeine re-increased aiNa and no longer had a negative inotropic action. 6. Increasing the Ca load by means of high [Ca]o (8.1 mM) increased force (+195%) and decreased aiNa, (-20.3%). Adding caffeine re-increased aiNa (+28.1%), but immediately decreased force (-32.3%). 7. Addition of pyruvate (10 mM) to caffeine increased force, as it does in the presence of Ca overload. 8. Noradrenaline (0.1-1 microM) decreased aiNa and increased contractile force. In its presence, caffeine decreased aiNa further and increased force. 9. It is concluded that caffeine increases aiNa, even during the negative inotropic effect. The decrease in force appears to depend on Ca load. Thus, caffeine no longer decreases force under conditions that decrease Ca load (Mn, high [K]0, TTX) and immediately decreases force when the Ca load is increased(high [Ca]0). However, in the presence of noradrenaline, caffeine decreases aiNa and markedly increases force, as the Ca load is increased, but Ca can be removed from the cytoplasm into the SR.