Genetic association between Ca2+-ATPase activity and audiogenic seizures in mice

Ca2+-ATPase activity was studied in fresh brain stem homogenates of the audiogenic seizure (AGS)-resistant C57BL/6 and AGS-susceptible DBA/2 inbred strains and in 21 B6 X D2 recombinant inbred strains. A highly significant negative correlation was found between Ca2+-ATPase activity and AGS susceptibility among these strains. In general, strains with low Ca2+-ATPase activities were more AGS-susceptible than strains with high activities. Further, Ca2+-ATPase activity appears to be influenced by a major gene associated with the Ah locus. This gene is designated Caa for Ca2+-ATPase activity and is different from Ias, which is closely linked to the Ah locus. Ias influences AGS spread by a yet unknown biochemical mechanism, whereas Caa may influence AGS susceptibility by regulating Ca2+-ATPase activity in brain tissue.