Effect of palytoxin on the sodium–potassium pump: model and simulation

We propose a reaction model for the palytoxin–sodium–potassium (PTX–Na⁺/K⁺) pump complex. The model, which is similar to the Albers–Post model for Na⁺/K⁺-ATPase, is used to elucidate the effect of PTX on Na⁺/K⁺-ATPase during the enzyme interactions with Na⁺ and/or K⁺ ions. Conformational substates and reactions for the pump are incorporated into the Albers–Post model to represent enzymes with or without bound PTX. A mathematical model based on the reaction scheme is used in simulations modeling experimental studies of PTX-induced ionic currents. Our simulations suggest that (i) extracellular Na⁺ as well as K⁺ promotes PTX-induced channel blockage; (ii) extracellular K⁺ accelerates PTX unbinding; and (iii) K⁺ occlusion in the PTX–pump complex is essential for describing the PTX-induced current dynamics.