title: Distribution of inositol-1,4,5-trisphosphate receptor isotypes and ryanodine receptor isotypes during maturation of the rat hippocampus.
abstract: Activation of inositol-1,4,5-trisphosphate receptors (InsP(3)Rs) and ryanodine receptors (RyRs) can lead to the release of Ca(2+) from intracellular stores and propagating Ca(2+) waves. Previous studies of these proteins in neurons have focused on their distribution in adult tissue, whereas, recent functional studies have examined neural tissue extracted from prenatal and young postnatal animals. In this study we examined the distribution of InsP(3)R isotypes 1-3 and RyR isotypes 1-3 in rat hippocampus during postnatal maturation, with a focus on InsP(3)R1 because it is most prominent in the hippocampus. InsP(3)R1 was observed in pyramidal cells and granule cells, InsP(3)R2 immunoreactivity was observed in perivascular astrocytes and endothelial cells, and InsP(3)R3 immunoreactivity was detected in axon terminals located in stratum pyramidale of CA1 and microvessels in stratum radiatum. RyR1 immunolabeling was enriched in CA1, RyR2 was most intense in CA3 and the dentate gyrus, and RyR3 immunolabeling was detected in all subfields of the hippocampus, but was most intense in stratum lacunosum-moleculare. During maturation from 2 to 10 weeks of age there was a shift in InsP(3)R1 immunoreactivity from a high density in the proximal apical dendrites to a uniform distribution along the dendrites. Independent of age, InsP(3)R1 immunoreactivity was observed to form clusters within the primary apical dendrite and at dendritic bifurcations of pyramidal neurons. As CA1 pyramidal neurons matured, InsP(3)R1 was often co-localized with the Ca(2+) binding protein calbindin D-28k. In contrast, InsP(3)R1 immunolabel was never co-localized with calbindin D-28k immunopositive interneurons located outside of stratum pyramidale or with parvalbumin, typically found in hippocampal basket cells, suggesting that InsP(3)R1s do not play a role in internal Ca(2+) release in these interneurons. These findings should help to interpret past functional studies and inform future studies examining the characteristics and consequences of InsP(3)R-mediated internal Ca(2+) release and Ca(2+) waves in hippocampal neurons.
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: D N
authors.initials: DN
authors.lastname: Hertle
authors.forename: M F
authors.initials: MF
authors.lastname: Yeckel
mesh_terms: D000818:Animals; D064026:Calbindins; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011940:Receptor Aggregation / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
chemical_list: D064026:Calbindins; D015220:Calcium Channels; C506928:ITPR2 protein, rat; D053496:Inositol 1,4,5-Trisphosphate Receptors; C488910:Itpr1 protein, rat; D008562:Membrane Glycoproteins; D010320:Parvalbumins; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D064030:S100 Calcium Binding Protein G; D002118:Calcium