Differential immunohistochemical localization of inositol 1,4,5-trisphosphate- and ryanodine-sensitive Ca²⁺ release channels in rat brain

Ca²⁺ release from inositol 1,4,5-trisphosphate(IP₃)-sensitive and ryanodine-sensitive intracellular Ca²⁺ stores is mediated by distinct proteins identified as IP³ receptors (IP³R) and ryanodine receptors (RyR), respectively. We have compared the immunohistochemical localizations of IP³R and RyR in the brain at the light and electron microscopic levels and have also evaluated the distribution of the major brain intracellular Ca²⁺-pumping ATPase. IP₃R and RyR occur in overlapping populations of neurons in widespread areas of the brain, but labeling is distinct in a number of areas. For example, IP₃R is enriched in cerebellar Purkinje cells and hippocampal CA1 pyramidal cells, while RyR is present at relatively low levels in these cells. RyR is most enriched in the dentate gyms and CA3/4 areas of the hippocampus, where IP₃R levels are low. In the cortex, IP₃R is found in pyramidal cell bodies and proximal dendrites, whereas RyR is located predominantly in long, thin apical dendrites of pyramidal cells. In deep cerebellar nuclei, RyR is located in cell bodies that appear devoid of IP₃R, whereas IP₃R is enriched in terminals surrounding cell bodies. Electron microscopy in the hippocampus reveals RyR in axons, dendritic spines, and dendritic shafts near dendritic spines while IP₃R is primarily identified in dendritic shafts and cell bodies. These results suggest that the IP₃- and ryanodine-sensitive Ca²⁺ pools have largely distinct roles in controlling intracellular Ca²⁺ levels, though in some sites they may interact to varying degrees.