Calmodulin mediates calcium-dependent inactivation of the cerebellar type 1 inositol 1,14,5-trisphosphate receptor

The dependency of purified mouse cerebellar type 1 inositol 1,4,5-trisphosp hate receptor (IP(3)R1)/Ca2+ channel function on cytoplasmic Ca2+ was exami ned. In contrast to the channels in crude systems, the purified IP(3)R1 rec onstituted into planar lipid bilayers did not show the bell-shaped dependen ce on Ca2+. It was activated with increasing Ca2+ sublinearly without inhib ition even up to 200 mu M. The addition of calmodulin to the cytoplasmic si de inhibited the channel at high Ca2+ concentrations. Calmodulin antagonist s reversed the Ca2+-dependent inactivation of the native channels in cerebe llar microsomes. These results indicate that the bell-shaped dependence on cytoplasmic Ca2+ is not an intrinsic property of the IP(3)R1, and the Ca2+- dependent inactivation is directly mediated by calmodulin.