Changes of KCl sensitivity of proliferating neural progenitors during in vitro neurogenesis

The effects of KCl-treatment on the survival and proliferation of NE-4C self-renewing neural progenitor cells were investigated during early phases of in vitro induced neurogenesis. NE-4C cells, derived from the anterior brain vesicles of embryonic mouse (E9), divided continuously under non-inducing conditions, but acquired neuronal features within 6 days, if induced by all-trans retinoic acid (RA). During the first 2 days of induction, the cells went on proliferating and did not show signs of morphological differentiation. In this stage, the resting membrane potential of RA-induced cells adopted more negative values in comparison to non-induced ones. Despite the increased membrane polarity and K+ conductance, addition of 20-50 mM KCl failed to elicit inward Na+ currents and did not induce an increase in the intracellular Ca+ level. Long-term treatment with 25 mM KCl, on the other hand, resulted in a selective loss of cells committed to neuronal fate by both decreasing the rate of cell proliferation and increasing the rate of cell death. The data indicate that the viability and proliferation of neural progenitors are influenced by extracellular K+-level in a differentiation stage-dependent manner.