The Na,K-ATPase hypothesis for bipolar illness

A cellular model for bipolar illness is presented. It is propounded that alterations in the activity of the membrane sodium- and potassium-activated adenosine triphosphatase pump (Na,K-ATPase) may be responsible for alterations in neuronal excitability and activity. Specifically, a reduction in Na,K-ATPase activity can lead to both mania and depression by increasing membrane excitability and decreasing neurotransmitter release, respectively. Supporting evidence is reviewed, and clinical and research implications are discussed.