MULTIPLE TYPES OF RYANODINE RECEPTOR CA2+ RELEASE CHANNELS ARE DIFFERENTIALLY EXPRESSED IN RABBIT BRAIN

The neuronal Ca2+ signal is induced by a rise in the intracellular fre e Ca2+ concentration ([Ca2+](i)), and is thought to be important for h igher brain function. Dynamic changes in [Ca2+](i) are affected by the spatial distributions of various Ca2+-increasing molecules (channels and receptors). The ryanodine receptor (RyR) is an intracellular chann el through which Ca2+ is released from intracellular stores. To define the contribution of neuronal Ca2+ signaling via the RyR channel, we e xamined RyR type-specific gene expression in rabbit brain by in situ h ybridization histochemistry. The neuronal RyR was composed of three di stinct types, two types dominant in skeletal (sRyR) and cardiac (cRyR) muscle, respectively, and a novel brain type (bRyR). sRyR was disting uished by its high level of expression in cerebellar Purkinje cells. c RyR was predominantly expressed throughout nearly the entire brain, an d was characterized by its markedly high level of expression in the ol factory nerve layer, layer VI of the cerebral cortex, the dentate gyru s, cerebellar granule cells, the motor trigeminal nucleus, and the fac ial nucleus. bRyR expression was the least widely distributed througho ut the brain, and was high in the hippocampal CA1 pyramidal layer, cau date, putamen, and dorsal thalamus. This investigation demonstrates th at the heterogeneous distribution of neuronal RyRs may be implicated i n distinct Ca2+-associated brain functions. Moreover, it should be not ed that cRyR, a typical CICR channel, is distributed widely throughout the brain, suggesting that in a variety of cell types, the amplificat ion of neuronal Ca2+ signals is functionally accompanied by a rise in [Ca2+](i), such as Ca2+ influx stimulated by neuronal activity. This w idespread distribution of the neuronal RyR family indicates that Ca2signals via the intracellular stores should be considered in studies o f neuronal Ca2+ dynamics.