Calcium ATPase activities in synaptic plasma membranes of seizure-prone mice

Audiogenic seizure (AGS)-susceptible DBA/2 (D2) mice have a significant reduction in brain Ca2+-ATPase activity compared to AGS-resistant C57BL/6 (B6) mice. This reduction is inherited together with AGS susceptibility in B6 X D2 recombinant inbred strains. The Ca2+-ATPase reduction occurs in microsomes and synaptosomes, but not in mitochondria. This enzyme activity is measured at a high Ca2+ concentration (2 mM) with no added Mg2+ or EGTA. We further studied this Ca2+-ATPase activity and a Mg2+-dependent (Ca2+ + Mg2+)-ATPase activity in synaptic plasma membranes (SPM) from the B6 and D2 strains. Using EGTA or CDTA to adjust free Ca2+ concentrations, we measured Ca2+-ATPase activities at Ca2+ concentrations from 0.8 microM to 436 microM. The Ca2+-ATPase activity is consistently lower in the D2 than in the B6 SPM over all Ca2+ concentrations. The basal Mg2+-ATPase activity measured at 2 mM MgCl2, is also lower in SPM of D2 than B6 mice. Calcium stimulates the basal Mg2+-ATPase activity to the same extent in the SPM of the B6 and the D2 mice. Maximum stimulation in both strains occurs at 150 microM added CaCl2 (buffered with 100 microM EGTA). Higher Ca2+ concentrations inhibit this ATPase activity similarly in both strains. The EGTA-EDTA washing of SPM significantly reduces by 50% of the (Ca2+ + Mg2+)-ATPase activities of both strains, whereas calmodulin treatment restored these activities. Neither of these treatments, however, has any noticeable effects on the Ca2+-ATPase activities of the strains.(ABSTRACT TRUNCATED AT 250 WORDS)