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Journal of Neuroscience, Vol 13, 3051-3063, Copyright © 1993 by Society for Neuroscience
Differential immunohistochemical localization of inositol 1,4,5- trisphosphate- and ryanodine-sensitive Ca2+ release channels in rat brain
AH Sharp, PS McPherson, TM Dawson, C Aoki, KP Campbell and SH Snyder
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
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.
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