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 free Ca²⁺ concentration ([Ca²⁺]_i), and is thought to be important for higher 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 channel through which Ca²⁺ is released from intracellular stores. To define the contribution of neuronal Ca²⁺ signaling via the RyR channel, we examined RyR type-specific gene expression in rabbit brain by in situ hybridization histochemistry. The neuronal RyR was composed of three distinct types, two types dominant in skeletal (sRyR) and cardiac (cRyR) muscle, respectively, and a novel brain type (bRyR). sRyR was distinguished by its high level of expression in cerebellar Purkinje cells. cRyR was predominantly expressed throughout nearly the entire brain, and was characterized by its markedly high level of expression in the olfactory nerve layer, layer VI of the cerebral cortex, the dentate gyrus, cerebellar granule cells, the motor trigeminal nucleus, and the facial nucleus. bRyR expression was the least widely distributed throughout the brain, and was high in the hippocampal CA1 pyramidal layer, caudate, putamen, and dorsal thalamus. This investigation demonstrates that the heterogeneous distribution of neuronal RyRs may be implicated in distinct Ca²⁺-associated brain functions. Moreover, it should be noted that cRyR, a typical CICR channel, is distributed widely throughout the brain, suggesting that in a variety of cell types, the amplification of neuronal Ca²⁺ signals is functionally accompanied by a rise in [Ca²⁺]_i, such as Ca²⁺ influx stimulated by neuronal activity. This widespread distribution of the neuronal RyR family indicates that Ca²⁺ signals via the intracellular stores should be considered in studies of neuronal Ca²⁺ dynamics.