The Relation Between Contraction and Intracellular Sodium in Voltage‐Clamped Sheep Purkinje Fibers

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Abstract
Contraction and Intracellular Sodium. Intracellular sodium activity (aiNa) and contraction were simultaneously recorded in voltage‐clamped sheep Purkinje fibers while the sodium‐potassium pump was inhibited with strophanthidin or low potassium. Exposures to low (1.5×10−7M) and high (10−5M) doses of strophanthidin resulted in aiNa and contraction increasing together. However, when strophanthidin was washed off, aiNa recovered more slowly than contraction. Due to this lag of aiNa behind contraction, there was hysteresis in the relation between contraction and aiNa. We compared strophanthidin exposures in voltage‐clamped fibers to those in unclamped fibers with action potentials. The lack of association between contraction and aiNa was less when fibers were clamped. We conclude that some of the dissociation previously reported in unclamped fibers was due to changes of membrane potential with strophanthidin. Using voltage clamp, we also compared the effect of different doses of strophanthidin applied to the same fiber. Higher doses of strophanthidin caused a larger rise of contraction for a similar increase of aiNa. Higher doses, which inhibit the Na‐K pump to a greater extent, also resulted in a faster rate of rise of aiNa. Inhibition and reactivation of the Na‐K pump with bathing potassium (or rubidium) also resulted in hysteresis between contraction and aiNa. A greater reduction of potassium caused a larger rise of contraction for a similar rise of aiNa. Lower potassium inhibits the Na‐K pump more completely and results in a faster rate of rise of aiNa. Although the absolute rise of aiNa with strophanthidin or low potassium is related to the increase of contraction, we conclude that this is not the only factor. The inotropic effect of these agents is also related to the rate at which aiNa rises; when the rate of rise is large, a given level of aiNa is associated with a larger contraction. Such behavior may be compatible with the presence of aiNa gradients from the subsarcolemmal space to the bulk cytoplasm during pump inhibition.