Critical interval of somal calcium transient after neurite transection determines B 104 cell survival.
Nerve cells may survive or die after axonal or dendritic transection. After neurite transection near (<50 mum) the cell body of Fura-2-loaded B 104 neuroblastoma (rat brain-derived) cells, the somal calcium concentration (SCC) undergoes a three-phase transient change: a rapid (0-0.15-min post-transection [PT]) rise phase, followed by an early (0.15--1.5-min PT) rapid decay phase, and succeeded by a late (1.5-60-min PT) slower decay phase that restores SCC to preinjury levels. The SCC in a critical interval (1.5-12.5 min PT) of the third transient phase correlates with cell fate, i.e., most transected cells that exclude dye (restore a barrier) and die have a significantly higher (P<0.005) SCC in this critical interval than do transected cells that exclude dye and survive at 24-hr PT. Loading BAPTA (chelation of somal Ca(2+)) before, but not after, the critical interval increases the percentage of cells that survive compared to that of cells transected without BAPTA loading. Furthermore, most transected cells that die despite successful barrier restoration exhibit characteristics consistent with apoptosis initiated during the critical interval of the SCC, including caspase activation and plasmalemmal phosphatidylserine translocation. These data suggest that decreased cell survival for injuries near the soma is due to Ca(2+)-initiated apoptosis during the critical interval of the third phase of the SCC transient. (c) 2005 Wiley-Liss, Inc.
Nguyen
Michael P
MP
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas.
Bittner
George D
GD
Fishman
Harvey M
HM
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019771:Axotomy; D020013:Calcium Signaling / Q000502:physiology*; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D003470:Culture Media; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D016501:Neurites / Q000502:physiology*; D010718:Phosphatidylserines / Q000378:metabolism; D051381:Rats; D012996:Solutions
D061945:Caspase Inhibitors; D002614:Chelating Agents; D003470:Culture Media; D004791:Enzyme Inhibitors; D010718:Phosphatidylserines; D012996:Solutions; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid