Voltage-gated potassium (K_v) channels are among the earliest ion channels to appear during brain development, suggesting a functional requirement for proper proliferation and differentiation of immature progenitor cells. We tested this hypothesis, using human neural progenitor cells (hNPCs) as an in vitro model system. In proliferating hNPCs a broad spectrum of K_v channel subtypes was identified. In whole-cell patch-clamp recordings K_v currents were separated into a large transient component characteristic for fast-inactivating A-type potassium channels and a sustained component produced by delayed-rectifying channels. Both K_v currents were differentially inhibited by selective neurotoxins like margatoxin and a-dendrotoxin and also less specific antagonists like tetraethylammonium chloride, 4-aminopyridine and quinidine. The density of both currents changed during differentiation, while their voltage dependencies were not altered. Chronic inhibition of the A-type currents severely disturbed the cell cycle and precluded proper hNPC proliferation, while blockade of delayed-rectifiers did not. These novel findings suggest that even A type potassium currents are essential for proliferation and the development of immature multipotent hNPCs.