Bioelectric State and Cell Cycle Control of Mammalian Neural Stem Cells

Julieta Aprea,Federico Calegari

doi:10.1155/2012/816049

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.

Highlights

An extensive literature has described the features and properties of bioelectric gradients and signaling in a variety of tissues of many species during development, adulthood, and regeneration [1,2,3,4,5]
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 involved in controlling proliferation and differentiation of nonexcitable somatic stem cells
Less investigated is whether similar parameters may play a role in controlling the switch of neural stem and progenitor cells from proliferative to neurogenic divisions but various evidences have accumulated in recent years making this possibility likely; in particular, when considering the multiple factors coupling bioelectric gradients and cell cycle progression [1, 7, 9, 10] as well as the effects of cell cycle length on proliferation versus differentiation of neural, and other somatic, stem cells [11, 12]

Summary

Introduction

An extensive literature has described the features and properties of bioelectric gradients and signaling in a variety of tissues of many species during development, adulthood, and regeneration [1,2,3,4,5]. In particular for the developing nervous system, it has become clear that the concerted action of membrane channels and ion pumps establishing a resting membrane potential (Vmem) and other bioelectric parameters plays important roles in migration, survival, maturation, and functionality of newborn neurons [6,7,8]. During embryonic development of the mammalian cortex, polarized radial-glial cells, referred to as apical progenitors (AP) forming the ventricular zone (VZ), progressively switch from divisions that generate additional AP to divisions that generate more committed, neurogenic progenitors leaving the VZ to form the subventricular zone (SVZ) at its pial, or basal, boundary; the name basal progenitors (BP) [13, 14]. In mammalian NSC of the developing embryo without discussing other bioelectric features, such as capacitance and input resistance, or additional roles of ion channels and metabotropic transporters involved in intracellular Ca2+ signaling, that were discussed elsewhere [1,2,3,4,5,6,7,8]

Establishing a Resting Membrane Potential in NSC

Membrane Potential and Proliferation versus Differentiation of NSC

Conclusions