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 "V_max" 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.