Putative receptor for inositol 1,4,5-trisphosphate similar to ryanodine receptor

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Abstract
INOSITOL 1,4,5-trisphosphate (Ins(l,4,5)P3) serves as an intracellular second messenger for several neurotransmitters, hormones and growth factors by initiating calcium release from intracellular stores1,2. A cerebellar Ins(l,4,5)P3 receptor has been characterized biochemically3,4 and shown by immunocytochemistry to be present in intracellular membranes in Purkinje cells5. We show that a previously described Purkinje-cell messenger RNA6 encodes a protein of relative molecular mass 260,000 (260 K) with the same properties as the cerebellar Ins(l,4,5)P3 receptor. Its sequence is partially homologous to the skeletal muscle ryanodine receptor7. By immunocytochemistry and electron microscopy the protein is shown to be present in all parts of the endoplasmic reticulum, including those that extend into axon terminals and dendritic spines. Our results indicate that gated calcium release from intracellular stores in muscle and Purkinje cells uses similar calcium-channel proteins localized in analogous intracellular compartments. This implies that the intracellular calcium stores in the endoplasmic reticulum of neurons extend into presynaptic terminals and dendritic spines where they may play a direct role in regulating the efficacy of neurotransmission.