The effect of heart rate on the membrane responsiveness of rabbit atrial muscle.

The maximum rate of rise of action potentials in myocardial fibers of the rabbit atrium decreases with an increase in heart rate. This decrease of the dV/dt max is accompanied by a decrease of the diastolic transmembrane potential prior to the moment of activation (take-off potential). Comparison of the membrane responsiveness curve (relation between dV/dt max and take-off potential) as measured by varying the extracellular potassium concentration at a fixed rate of stimulation, with the effect of changes in the frequency of stimulation on dV/dt max and take-off potential made clear that the fall in dV/dt max after a sudden increase in heart rate was stronger than could be explained by the concomitant decrease of the take-off potential alone. This implicates that the membrane responsiveness itself is heart rate dependent. A possible explanation for this observation is that when heart rate is increased the active Na/K pump is not able to maintain the intracellular concentration of Na and K at the original level. Acceleration of the heart will lead to an intracellular loss of potassium and a gain of sodium. The first causes a diminishment of the diastolic membrane potential which according to the membrane responsiveness curve is attended with a decrease of the dV/dt max. The second results in a decrease of the sodium concentration gradient and therefore in a further reduction of the dV/dt max. This hypothesis was confirmed by experiments with ouabain added to the perfusion fluid. Ouabain, which is known to inhibit the Na/K pump, caused a decrease of both the take-off potential and dV/dt max that was completely comparable with the effects of an increase of the frequency of stimulation. In addition, observation of the time course of the changes in dV/dt max and membrane "resting" potential after a sudden change in the rate of stimulation, gave support to the electrogenic concept of the active Na/K pump in cardiac muscle.