Kinetics of the inhibition of the Na-K pump by tetrapropylammonium chloride

Abstract

1. The tetrapropylammonium ion (TPA) acts as a mixed-type (with K) inhibitor of the Na-K pump. The kinetics of the process suggest that combination of the pump with a single TPA ion is sufficient for inhibition. 2. TPA inhibits the partial reactions of the Na-K pump (the uncoupled Na outflux, the Na-Na exchange, and K-K exchange). 3. TPA inhibits ouabain binding to the pump and this inhibitory effect is enhanced by external Na. The inhibitory effect of TPA on the pump rate is also promoted by external Na. 4. A Lineweaver-Burk plot of the reciprocal of the ouabain-sensitive K influx versus the reciprocal of the external K concentration is approximately a straight line if the measurements are made in Na-free solutions. TPA increases the apparent Michaelis constant (K 1/2) for K and the plot remains straight. 5. The Lineweaver-Burk plot is parabolic when the measurements are made in solutions which contain Na. TPA both increases the apparent K 1/2 for K and makes the curve more parabolic. 6. The characteristics of pump inhibition by TPA are similar to those for strophanthidin. In both cases the kinetic behaviour is consistent with a model in which the inhibitor binds: with greatest affinity to the pump form free of K; with less affinity to the pump form with a single bound K; and with least affinity to the pump form with two bound K.