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Voltage‐gated K + current: a marker for apoptosis in differentiating neuronal progenitor cells?
Author(s) -
Hribar Marusa,
Bloc Alain,
Medilanski Jeana,
Nüsch Lars,
EderColli Lorenza
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2004.03520.x
Subject(s) - apoptosis , microbiology and biotechnology , staurosporine , biology , stem cell , progenitor cell , programmed cell death , caspase , chemistry , signal transduction , biochemistry , protein kinase c
We investigated apoptosis during early stages of in vitro differentiation of neuronal precursors generated by embryonic day 14 (E14) mouse striata stem cells. Differentiation was in conditions of suboptimal growth factor supply. Apoptosis reached 10–15% of cells and affected proliferating as well as postmitotic cells, including TUJ1‐positive cells. Inhibition of apoptosis led to an increased proportion of TUJ1‐positive cells generated by stem cells. K + current was reported to be related to apoptosis. Outward K + currents were present in differentiating neuronal precursors that were consistent with delayed rectifier and transient A‐type currents. The amplitude of the delayed rectifier current varied during the first 4 days of stem cell differentiation. Current amplitude was greatly increased in the presence of staurosporine but reduced at elevated extracellular K + concentration. In addition, the amplitude of the current was significantly diminished by inhibiting several caspases, but not caspase 8. In Bax knock‐out transgenic neuronal precurors, K + current was not decreased after the first day but at later stages of cell differentiation. At this early stage, apoptosis of proliferating cells and of TUJ1‐positive cells was not reduced by the absence of Bax, but was by caspase 9 inhibition. Thus, activation of a delayed rectifier K + current in differentiating stem cells is related to apoptosis. Recordings of this current revealed that apoptosis at early stages of neuronal differentiation occurred in two phases that did not exhibit similar dependence on the proapoptotic protein Bax and that probably used different pathways.