Journal
CELL CALCIUM
Volume 96, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ceca.2021.102399
Keywords
Ca2+transients; Ca2+release channels; Endoplasmic reticulum; Ca2+release; Rat hippocampus
Categories
Funding
- Iniciativa Cientifica Milenio (ICM), Chile [P09-015-F]
- Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT), Chile [BMBF-180051]
- International Joint Federal Ministry of Education and Research (BMBF), Germany [BMBF-180051]
- Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT), Chile [FONDECYT-1181823, FONDECYT-1140617, FONDECYT-1140545, FONDECYT-1170058, FONDECYT-3110157]
- CONICYT BECAS, Chile [74150080]
- Fondo de Fomento al Desarrollo Cientifico y Tecnologico (FONDEF), Chile [FONDEF-ID19I10334]
- Agencia Nacional de Investigacion y Desarrollo (ANID), Chile [ANID-COVID0733]
- US LACRN, USA
- [CONICYT-21120689]
- [CONICYT-21161086]
- [FONDECYT-3140447]
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Neuronal Ca2+ signals are essential for synaptic transmission and gene expression changes. Voltage-gated Ca2+ channels and N-methyl-D-aspartate receptors are important for Ca2+ entry during action potential firing. The endoplasmic reticulum (ER), including RyR and IP3R channels, contributes to Ca2+ signal generation in response to neuronal activity. The study investigates the role of RyR-mediated Ca2+ release in IP3-generated Ca2+ signals in dendrites and the potential impact of atlastin on Ca2+ signaling and ER-resident Ca2+ channel distribution.
Neuronal Ca2+ signals are fundamental for synaptic transmission and activity-dependent changes in gene expression. Voltage-gated Ca2+ channels and N-methyl-D-aspartate receptors play major roles in mediating external Ca2+ entry during action potential firing and glutamatergic activity. Additionally, the inositol-1,4,5trisphosphate receptor (IP3R) and the ryanodine receptor (RyR) channels expressed in the endoplasmic reticulum (ER) also contribute to the generation of Ca2+ signals in response to neuronal activity. The ER forms a network that pervades the entire neuronal volume, allowing intracellular Ca2+ release in dendrites, soma and presynaptic boutons. Despite its unique morphological features, the contributions of ER structure and of ERshaping proteins such as atlastin - an ER enriched GTPase that mediates homotypic ER tubule fusion - to the generation of Ca2+ signals in dendrites remains unreported. Here, we investigated the contribution of RyRmediated Ca2+ release to IP3-generated Ca2+ signals in dendrites of cultured hippocampal neurons. We also employed GTPase activity-deficient atlastin-2 (ATL2) mutants to evaluate the potential role of atlastin on Ca2+ signaling and ER-resident Ca2+ channel distribution. We found that pharmacological suppression of RyR channel activity increased the rising time and reduced the magnitude and propagation of IP3-induced Ca2+ signals. Additionally, ATL2 mutants induced specific ER morphological alterations, delayed the onset and increased the rising time of IP3-evoked Ca2+ signals, and caused RyR2 and IP3R1 aggregation and RyR2 redistribution. These results indicate that both RyR and ATL2 activity regulate IP3-induced Ca2+ signal dynamics through RyRmediated Ca2+-induced Ca2+ release, ER shaping and RyR2 distribution.
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