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The Journal of Neuroscience, July 1, 2002, 22(13):5344-5353
Distinct Intracellular Calcium Transients in Neurites and Somata Integrate Neuronal Signals
Friedrich W. Johenning1, 3, Michal Zochowski2, Stuart J. Conway4, Andrew B. Holmes4, Peter Koulen1, and Barbara E. Ehrlich1, 2 Departments of 1 Pharmacology and 2 Cellular and Molecular Physiology, Yale University, New Haven, Connecticut 06520, 3 Department of Neuroanatomy, University Hospital Eppendorf, 20246 Hamburg, Germany, and 4 Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom
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.
Key words: intracellular calcium signaling; inositol 1,4,5 trisphosphate; InsP3 receptor; ryanodine receptor; PC12 cells; neurite; soma
Copyright © 2002 Society for Neuroscience 0270-6474/02/22135344-10$05.00/0
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