title: Distinct intracellular calcium transients in neurites and somata integrate neuronal signals.
abstract: Intracellular calcium signals have distinct temporal and spatial patterns in neurons in which signal initiation and repetitive spiking occurs predominantly in the neurite. We investigated the functional implications of the coexpression of different isoforms of ryanodine receptors (RyR) and inositol 1,4,5-trisphosphate receptors (InsP3Rs) using immunocytochemistry, Western blotting, and calcium imaging in neuronally differentiated PC12 cells. InsP3R type III, an isoform that has been shown to be upregulated in neuronal apoptosis, is exclusively expressed in the soma, serving as a gatekeeper for high-magnitude calcium surges. InsP3R type I is expressed throughout the cell and can be related to signal initiation and repetitive spiking in the neurite. RyR types 2 and 3 are distributed throughout the cell. In the soma, they serve as amplifying molecular switches, facilitating recruitment of the InsP3R type III-dependent pool. In the neurite, they decrease the probability of repetitive spiking. Use of a cell-permeant analog of InsP3 suggested that regional specificity in InsP3 production and surface-to-volume effects play minor roles in determining temporal and spatial calcium signaling patterns in neurons. Our findings suggest that additional modulatory processes acting on the intracellular channels are necessary to generate spatially specific calcium signaling.
authors.affiliation: Departments of Pharmacology and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Johenning
authors.forename: Michal
authors.initials: M
authors.lastname: Zochowski
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Conway
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Holmes
authors.forename: Peter
authors.initials: P
authors.lastname: Koulen
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Ehrlich
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000032:analysis*; D020013:Calcium Signaling; D003593:Cytoplasm / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007700:Kinetics; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D020033:Protein Isoforms / Q000032:analysis; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis*; D011976:Receptors, Muscarinic / Q000032:analysis; D019837:Ryanodine Receptor Calcium Release Channel / Q000032:analysis*; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D011976:Receptors, Muscarinic; D019837:Ryanodine Receptor Calcium Release Channel; D019284:Thapsigargin; D020932:Nerve Growth Factor; D003620:Dantrolene