期刊
CELL CYCLE
卷 7, 期 20, 页码 3225-3234出版社
LANDES BIOSCIENCE
DOI: 10.4161/cc.7.20.6831
关键词
patch clamp; single-channel recordings; apoptosis; VDAC; hippocampal neurons; neural stem cells; sodium channels
类别
资金
- European Commission [CT-2003-506143]
- Swedish Research Council
- Karolinska Institutet
- Linkoping University
- County Council of Ostergotland
One of the earliest morphological changes occurring in apoptosis is cell shrinkage associated with an increased efflux of K(+) and Cl(-) ions. Block of K(+) or Cl(-) channels prevents cell shrinkage and death. Recently, we found evidences for the activation of a voltage-dependent anion channel in the plasma membrane (pl-VDAC) of a hippocampal cell line undergoing apoptosis. Nothing is known on pl- VDAC in apoptotic cell death of neural cells at different stages of differentiation. We have addressed this issue in primary cultures of differentiated hippocampal neurons and embryonic neural stem cells (NSCs). In control hippocampal neurons, pl- VDAC is closed but acts as an NADH-ferricyanide reductase, while in apoptotic neurons, pl- VDAC is opened and the enzymatic activity is increased. Anti-VDAC antibodies block pl- VDAC and prevent apoptosis, as well as the increase in enzymatic activity. Conversely, in NSCs, pl- VDAC is scarcely seen and there is no NADH-ferricyanide reductase activity. In agreement, anti-VDAC antibodies do not affect the apoptotic process. Instead, we find activation of a Na(+) channel that has low voltage dependency, a conductance of 26 pS, and is blocked by amiloride, which also prevents apoptosis. Thus, it appears that activation of pl- VDAC during apoptosis is a critical event in differentiated neurons, but not in NSCs.
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