Distinct intracellular calcium transients in neurites and somata integrate neuronal signals.
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.
Johenning
Friedrich W
FW
Departments of Pharmacology and Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520, USA.
Zochowski
Michal
M
Conway
Stuart J
SJ
Holmes
Andrew B
AB
Koulen
Peter
P
Ehrlich
Barbara E
BE
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
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