Physical Interaction between the lnositol 1, 4, 5-Trisphosphate Receptor and Ryanodine Receptor in Rat Cerebellum

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Many cell types, including cerebellar Purkinje cell, co-express the inositol 1, 4, 5-trisphosphate receptor and ryanodine receptor, the two classes of the intracellular Ca^<2+> release channel. Functional co-operation between these two intracellular Ca^<2+> release channels seems to exist in such cells. Spatial proximity of the two channels would be important for them to cooperate. Here we report that a physical interaction between subunits of the inositol 1, 4, 5-trisphosphate receptor and ryanodine receptor channel exists. Type 1 inositol 1, 4, 5-trisphosphate receptor subunit co-precipitated when type 2 ryanodine receptor subunit was immunoprecipitated from rat cerebellum membrane fraction by and, vice versa, type 2 ryanodine receptor subunit co-immunoprecipitated with type 1 inositol 1, 4, 5-trisphosphate receptor subunit. When protein complexes in the membrane fraction were dissociated into individual subunits prior to immunoprecipitation procedure, the co-immunoprecipitation of the two Ca^<2+> release channel subunits was abolished despite immunoprecipitating antibodies (specific for type 1 inositol 1, 4, 5-trisphosphate receptor or ryanodine receptor) still immunoprecipitated their respective antigen. Our results suggest a physical association of the inositol 1, 4, 5-trisphosphate receptor and ryanodine receptor, which would ensure the functional co-operation of the two intracellular Ca^<2+> release channels.