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Abnormal calmodulin-activated CaATPase in manic-depressive subjects.

H L Meltzer, S Kassir

    Journal of Psychiatric Research
    |January 1, 1982
    PubMed
    Summary

    Manic-depressive patients show abnormal calmodulin-activated calcium ATPase (CaATPase) activity in erythrocyte membranes. Lithium treatment appears to sensitize this enzyme to monovalent cations.

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    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.

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