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Abnormal calmodulin-activated CaATPase in manic-depressive subjects
Insights
Manic-depressive patients show abnormal calmodulin-activated calcium ATPase (CaATPase) activity in erythrocyte membranes. Lithium treatment appears to sensitize this enzyme to monovalent cations.
Area of Science:
- Biochemistry
- Neuroscience
- Cell Biology
Background:
- The calcium-dependent ATPase (CaATPase) in human erythrocyte membranes plays a crucial role in cellular calcium homeostasis.
- This enzyme exists in basal and calmodulin-activated forms, both susceptible to modulation by monovalent ions like lithium, sodium, and potassium.
- Alterations in CaATPase function have been implicated in various neurological and psychiatric conditions.
Purpose of the Study:
- To investigate potential biochemical abnormalities in erythrocyte membrane CaATPase in individuals with bipolar disorder (manic-depressive illness).
- To assess the impact of lithium carbonate treatment on CaATPase activity and its response to monovalent cations in this patient population.
Main Methods:
- Erythrocyte membranes were isolated from three groups: normal controls, manic-depressive patients treated with lithium carbonate, and manic-depressive patients not treated with lithium carbonate.
- The activity of the calmodulin-activated CaATPase was measured under varying concentrations of lithium, sodium, and potassium ions.
Main Results:
- Manic-depressive subjects, regardless of lithium treatment, exhibited greater activation of the calmodulin-dependent CaATPase with sub-optimal lithium concentrations compared to controls, suggesting an inherent biochemical abnormality.
- Both control and untreated manic-depressive groups showed lower enzyme activity with optimal sodium and potassium concentrations than the lithium-treated group, indicating lithium carbonate sensitizes the enzyme to these cations.
Conclusions:
- The findings strongly suggest that calmodulin-activated CaATPase is biochemically abnormal in individuals with manic-depressive illness.
- Lithium carbonate treatment appears to alter the sensitivity of erythrocyte membrane CaATPase to monovalent cations, potentially contributing to its therapeutic effects.
Abstract:
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.