DEFICIENCY OF A Ca²⁺‐ATPase IN BRAINS OF SEIZURE PRONE MICE

Abstract

Abstract– Ca 2+ ‐stimulated ATPase activity was studied in membrane enriched preparations from the brains of audiogenic seizure‐prone (DBA) and control (C57 and C3H) mice. The animals ranged in age from 7 to 60 days. Na + , K + ‐ATPase, 5′‐nucleotidase and p ‐nitrophenylphosphatase were assayed to evaluate membrane integrity. Ca 2+ ‐ATPase was significantly lower in DBA mice; notably during the period of maximal seizure sensitivity. Mg 2+ ‐ATPase somewhat followed the pattern shown by Ca 2+ ‐ATPase. Na + , K + ‐ATPase in DBA did not differ significantly from controls and there were no differences in either 5′‐nucleotidase or p‐nitrophenylphosphatase activities. Ca 2+ ‐ATPase kinetics experiments showed even more clearly the difference between DBA and control preparations. V max was consistently lower in DBA than in controls. The K m values appeared to fall into groupings suggestive of sequential synthesis of isozymes. Differences in the patterns of DBA and C57 just prior to the time of maximal seizure sensitivity are interpreted as reflecting failure to synthesize an isozyme or delay of its synthesis. The genesis of seizures through such an enzymatic defect may be related to the action of translocated ATP on the plasma membrane.