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Titolo:
Strain-dependent differences in calcium signaling predict excitotoxicity in murine hippocampal neurons
Autore:
Shuttleworth, CWR; Connor, JA;
Indirizzi:
Univ New Mexico, Sch Med, Dept Neurosci, Albuquerque, NM 87131 USA Univ New Mexico Albuquerque NM USA 87131 rosci, Albuquerque, NM 87131 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 12, volume: 21, anno: 2001,
pagine: 4225 - 4236
SICI:
0270-6474(20010615)21:12<4225:SDICSP>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
SPINAL-CORD NEURONS; PYRAMIDAL NEURONS; BRAIN-DAMAGE; KAINIC ACID; CELL-DEATH; IN-VITRO; ACTIVATION; GLUTAMATE; SLICE; RECEPTORS;
Keywords:
excitotoxicity; kainate; hippocampus; mouse strain; CA1 dendrite; calcium; optical indicator;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Shuttleworth, CWR Univ New Mexico, Sch Med, Dept Neurosci, 915 Camino de Salud NE, Albuquerque, NM 87131 USA Univ New Mexico 915 Camino de Salud NE Albuquerque NM USA 87131
Citazione:
C.W.R. Shuttleworth e J.A. Connor, "Strain-dependent differences in calcium signaling predict excitotoxicity in murine hippocampal neurons", J NEUROSC, 21(12), 2001, pp. 4225-4236

Abstract

Commonly used inbred murine strains differ substantially in their vulnerability to excitotoxic insults. We investigated whether differences in dendritic Ca2+ signaling could underlie the differential vulnerability of C57BL/6(resistant to kainate excitotoxicity) and C57BL/10 strains (vulnerable). Astriking difference was found in fine dendrite Ca2+ responses after kainate exposure. Ca2+ signals in distal dendrites were large in C57BL/10 neurons, and, if a threshold concentration of similar to1.5 muM was reached, a region of sustained high Ca2+ was established in the distal dendritic tree. This region then served as an initiation site for a degenerative cascade, producing high Ca2+ levels that slowly spread to involve the entire neuron andled to cell death. Dendritic Ca2+ signals in C57BL/6 neurons were much smaller and did not trigger these propagating secondary responses. Strain differences in dendritic Ca2+ signaling were also evident after tetanic stimulation of Schaffer collaterals. Ca2+ responses were much larger and peaked earlier in distal dendrites of C57BL/10 compared with those in C57BL/6. Neurons from both strains had similar membrane properties and responded to kainate with intense action potential firing. Degenerative Ca2+ responses were seen in both strains if soma Ca2+ could be sustained above 1.5 muM. The early phases of secondary Ca2+ responses were attributable to Ca2+ influx and were abolished rapidly by buffered zero Ca2+ saline. Taken together, these data indicate that the substantial difference in Ca2+ signals in fine distaldendrites and in the initiation of spreading secondary responses may underlie the selective vulnerability of these neurons to excitotoxic insults.

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Documento generato il 29/03/20 alle ore 12:10:57