| Sumario: | Intracellular sodium activity (aNai) 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 (1.5x10-7M) and high (10-5M) doses of strophanthidin resulted in aNai and contraction increasing together. However, when strophanthidin was washed off, aNai recovered more slowly than contraction. Due to this lag of aNai behind contraction, there was hysteresis in the relation between contraction and aNai. We compared strophanthidin exposures in voltage-clamped fibers to those in unclamped fibers with action potentials. The lack of association between contraction and aNai 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 aNai. Higher doses, which inhibit the Na-K pump to a greater extent, also resulted in a faster rate of rise of aNai. Inhibition and reactivation of the Na-K pump with bathing potassium (or rubidium) also resulted in hysteresis between contraction and aNai. A greater reduction of potassium caused a larger rise of contraction for a similar rise of aNai. Lower potassium inhibits the Na-K pump more completely and results in a faster rate of rise of aNai. Although the absolute rise of aNai 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 aNai rises; when the rate of rise is large, a given level of aNai is associated with a larger contraction. Such behavior may be compatible with the presence of aNai a gradients from the subsarcolemmal space to the bulk cytoplasm during pump inhibition.
|
|---|