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

Abstract

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 Ca(2+)-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 gyrus 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.

Muscarinic stimulation of synaptic activity by protein kinase C is inhibited by adenosine in cultured hippocampal neurons

“…It is worth noting that previous immunohistochemical experiments revealed a nonuniform distribution of the IP 3 -receptors in hippocampal cells. They are mainly located in the dendritic shaft (but not in spines) and are rarely found in axons or nerve terminals (24,36). Our results seem to differ from those showing that in CA1 hippocampal neurons BAPTA loading prevented the potentiating effect of acetylcholine on Nmethyl-D-aspartate responses (37).…”

Presynaptic calcium stores underlie large-amplitude miniature IPSCs and spontaneous calcium transients

“…Role of ryanodine receptors Ryanodine receptors (RyRs) are widely distributed in the mammalian brain 24 , so we looked for them in synaptic terminals of cerebellar interneurons. Immunohistochemistry shows RyR staining in somata of Purkinje cells and basket cells, but not in terminals of basket cells or any other neuron 25,26 . Postsynaptic staining may have obscured possible staining of adjacent presynaptic terminals, and pre-and postsynaptic RyRs may be of different subtypes and therefore may react with different antibodies.…”

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

“…Recently a splice variant of RyR2 was identified in the heart that increases susceptibility to apoptosis (Valdivia 2007). RyR2 is also expressed at high levels in Purkinje cells of cerebellum and cerebral cortex (Lai et al 1992;Nakanishi et al 1992;Sharp et al 1993;Furuichi et al 1994) and in low levels in stomach, kidney, adrenal glands, ovaries, thymus, and lungs Giannini et al 1995).…”