Kir and Kv channels regulate electrical properties and proliferation of adult neural precursor cells

The functional significance of the electrophysiological properties of neural precursor cells (NPCs) was investigated using dissociated neurosphere-derived NPCs from the forebrain subventricular zone (SVZ) of adult mice. NPCs exhibited hyperpolarized resting membrane potentials, which were depolarized by the K+ channel inhibitor, Ba2+. Pharmacological analysis revealed two distinct K+ channel families: Ba2+-sensitive Kir channels and tetraethylammonium (TEA)-sensitive Kv (primarily KDR) channels. Ba2+ promoted mitogen-stimulated NPC proliferation, which was mimicked by high extracellular K+, whereas TEA inhibited proliferation. Based on gene and protein levels in vitro, we identified Kir4.1, Kir5.1 and Kv3.1 channels as the functional K+ channel candidates. Expression of these K+ channels was immunohistochemically found in NPCs of the adult mouse SVZ, but was negligible in neuroblasts. It therefore appears that expression of Kir and Kv (KDR) channels in NPCs and related changes in the resting membrane potential could contribute to NPC proliferation and neuronal lineage commitment in the neurogenic microenvironment.