Bioelectric state and cell cycle control of Mammalian neural stem cells

Abstract

The concerted action of ion channels and pumps establishing a resting membrane potential has been most thoroughly studied in the context of excitable cells, most notably neurons, but emerging evidences indicate that they are also involved in controlling proliferation and differentiation of nonexcitable somatic stem cells. The importance of understanding stem cell contribution to tissue formation during embryonic development, adult homeostasis, and regeneration in disease has prompted many groups to study and manipulate the membrane potential of stem cells in a variety of systems. In this paper we aimed at summarizing the current knowledge on the role of ion channels and pumps in the context of mammalian corticogenesis with particular emphasis on their contribution to the switch of neural stem cells from proliferation to differentiation and generation of more committed progenitors and neurons, whose lineage during brain development has been recently elucidated.

Figure 1

Scheme representing cell types in the developing mammalian cortex with (from top to bottom) neurons, basal (BP), and apical (AP) progenitors forming the cortical plate (CP), intermediate (IZ), subventricular (SVZ), and ventricular (VZ) zones, respectively. Lineages are depicted (arrows). Note the distinction between apical and basolateral plasma membrane of AP establishing the apicobasal polarity of the developing cortex.

Figure 2

Effects upon manipulation of ion channels or extracellular ionic composition on the proliferation of NSC. Green and red arrows indicate increased or decreased proliferation, respectively, as deduced from incorporation of thymidine analogues or number of neurons in the adult striatum (1) or motor cortex (2). Agonists and antagonists used (Psora-4 = 5-(4-phenylbutoxy)psoralen; TEA = tetraethylammonium chloride; QND = quinidine; DTX = α-dendrotoxin; FSK = forskolin; 4-AP = 4-aminopyridine; PTX = phrixotoxin; BMI = biculline methionine; D-APV = D(-)-2-amino-5-phosphonopentanoicacid; CNQX = 6-cyano-7-dinitroquinoxaline-2,3-dione; NQBX = 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzol(f)-quinoxaline-7-sulfonamide) as well as source of NSC form different species (r = rat; h = human; m = mouse), developmental stage (E = embryonic day; W = embryonic week), or region (mid = midbrain; Cx = cortex; LGE = lateral ganglionic eminence; Hp = hippocampus; VZ = ventricular zone; SVZ = subventricular zone) are indicated. *reduced viability; **only in the presence of bFGF; O-2A = oligodendrocyte progenitors.