Stimulation of Na,K-activated adenosine triphosphatase and active transport by low external K+ in a rat liver cell line

Exposure of ARL 15 cells, an established line from adult rat liver, to concentrations of external K+ below 1 mM caused a rapid fall in intracellular K+ and a corresponding rise in intracellular Na+ that became maximal within 12 h. Upon continued exposure to low external K+, these initial changes were followed by a striking recovery such that, by 24 h, intracellular Na+ and K+ concentrations approached their control values. Concomitant with this recovery, there was a substantial increase in Na,K-ATPase specific activity that was detectable at 12 h and maximal at 24 h. After restoration of the external K+ concentration, the elevated level of enzyme activity showed little change for at least 24 h. In contrast, restoration of external K+ resulted in a rapid rise in intracellular K+ and a fall in Na+ such that within 30 min the Na+/K+ ratio was lower than in control cells. This overshoot, together with a demonstrated increase in active 86Rb+ uptake under "Vmax" conditions, confirms that the enhancement in Na,K-ATPase specific activity in response to low external K+ represents an increase in functional Na,K pumping capacity.