FIGURE 2.

Na⁺/K⁺ ATPase activity is lower in BD patients and animal models of mania. The enzyme activity is dependent on the fluidity of the membrane, which is lower when the unsaturated/saturated fatty acids ratio at the membrane is decreased, as is the case of BD patients. Moreover, the alteration in the n3/n6 ratio also can modify the membrane fluidity and in turn decrease the Na⁺/K⁺ ATPase activity. This alteration in lipid composition could be related to the reported lower activity of the enzyme in patients, and it is likely that the lowered activity of the enzyme is related to the symptomatology of BD because reducing the activity of the enzyme pharmacologically with ouabain or by the genetic alteration of the enzyme (Atp1a3 mutant) induces a manic phenotype, with behavioral changes related to mania together with increased oxidative stress and reduction in BDNF expression. Furthermore, some BD patients have been reported to express variants of the enzyme, and also expression of the enzyme is altered in key regions of the limbic system. Altogether the evidence points toward a role for Na⁺/K⁺ ATPase in the etiology of BD. Unsaturated/saturated fatty acids ratio at the membrane also affects de hydrophobic thickness of the membrane which in turns can affect the pump activity.