Abnormal calmodulin-activated CaATPase in manic-depressive subjects.

CaATPase of human erythrocyte membranes exists in both a basal and a calmodulin-activated form, each of which can be further activated by monovalent ions such as sodium, potassium or lithium. We have measured the extent of such activation in erythrocyte membranes obtained from 14 manic-depressive outpatients under treatment with lithium carbonate, nine such patients not treated with lithium carbonate, and eight normal controls. The principal findings were as follows: (1) when further activation of the calmodulin-dependent enzyme was measured in the presence of a sub-optimal concentration of lithium ions, greater activation was observed for all manic-depressive subjects, whether or not treated with lithium carbonate, than for controls. We interpret this observation to mean that a biochemical abnormality exists in this patient population with respect to controls; (2) when activation was measured in the presence of optimal concentrations of sodium and potassium ions, the control and the untreated patient groups each showed lesser activity than the lithium carbonate treated groups, indicating that this treatment sensitized the membrane enzyme to monovalent cations. Overall, both of these results indicate that calmodulin-activated CaATPase is abnormal in manic-depressive patients.