Characterization of Ionic Currents in Human Neural Stem Cells

Abstract

The profile of membrane currents was investigated in differentiated neuronal cells derived from human neural stem cells (hNSCs) that were obtained from aborted fetal cortex. W hole-cell voltage clamp recording revealed at least 4 different currents: a tetrodotoxin (TTX)-sensitive Na + current, a hyperpolarization-activated inward current, and A-type and delayed rectifier-type K + outward currents. Both types of K + outward currents were blocked by either 5 mM tetraethylammonium (TEA) or 5 mM 4-aminopyridine (4-AP). The hyperpolarization-activated current resembled the classical K + inward current in that it exhibited a voltage-dependent block in the presence of external Ba 2+ (30μ M) or Cs + (3μ M). However, the reversal potentials did not match well with the predicted K + equilibrium potentials, suggesting that it was not a classical K + inward rectifier current. The other Na + inward current resembled the classical Na + current observed in pharmacological studies. The expression of these channels may contribute to generation and repolarization of action potential and might be regarded as functional markers for hNSCs-derived neurons.

Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice

“…While voltage-gated calcium currents can be detected in neural stem and progenitor cells, only L-type calcium channels have hitherto been identified, which are not known to be blocked by ZD7288 (46)(47)(48). Furthermore, voltage-gated sodium channels are primarily associated with the differentiation, but not the proliferation, of neural progenitor cells (47)(48)(49)(50)(51)(52)(53)(54). Therefore, both the dominant-negative transgenic strategy and the pharmacological block of Ih are likely to have affected the same HCN current-dependent mechanism.…”