The Segregated Expression of Voltage-Gated Potassium and Sodium Channels in Neuronal Membranes: Functional Implications and Regulatory Mechanisms.

Maël Duménieu,Michael R Kreutz,Jeffrey Lopez-Rojas,Marie Oulé

doi:10.3389/fncel.2017.00115

Abstract

Neurons are highly polarized cells with apparent functional and morphological differences between dendrites and axon. A critical determinant for the molecular and functional identity of axonal and dendritic segments is the restricted expression of voltage-gated ion channels (VGCs). Several studies show an uneven distribution of ion channels and their differential regulation within dendrites and axons, which is a prerequisite for an appropriate integration of synaptic inputs and the generation of adequate action potential (AP) firing patterns. This review article will focus on the signaling pathways leading to segmented expression of voltage-gated potassium and sodium ion channels at the neuronal plasma membrane and the regulatory mechanisms ensuring segregated functions. We will also discuss the relevance of proper ion channel targeting for neuronal physiology and how alterations in polarized distribution contribute to neuronal pathology.

Highlights

The neuronal cytoarchitecture defines two main cellular compartments: dendrites that receive, integrate and propagate synaptic input (Häusser et al, 2000; Magee and Johnston, 2005; Stuart and Spruston, 2015) and the axon that eventually converts these processed inputs into variable patterns of action potential (AP), with fast and robust transmission to distant postsynaptic targets
Findings from this study indicate that CaMKII-dependent Ser39 and Ser232 phosphorylation of the SAP97 protein increases the expression of the Kv4.2 channel at dendritic spines (Gardoni et al, 2007), suggesting that CaMKII-dependent SAP97 phosphorylation is important for synaptic trafficking of Kv4.2 channel (Figure 2B)
Proper expression, segregated distribution and the functional state of Nav and Kv channel isoforms at axonal and somatodendritic domains, and within its subcellular compartments, are critical determinants of the electrogenic properties of a neuron as illustrated by the multiple pathologies associated with Nav and Kv channels (Smith, 2007; Mantegazza et al, 2010; Catterall, 2012; Savio-Galimberti et al, 2012; Shah and Aizenman, 2014; O’Malley and Isom, 2015; Kruger and Isom, 2016; Villa and Combi, 2016)

Summary

INTRODUCTION

The neuronal cytoarchitecture defines two main cellular compartments: dendrites that receive, integrate and propagate synaptic input (Häusser et al, 2000; Magee and Johnston, 2005; Stuart and Spruston, 2015) and the axon that eventually converts these processed inputs into variable patterns of action potential (AP), with fast and robust transmission to distant postsynaptic targets. We focus on specific potassium and sodium VGCs: Kv1, Kv4.2 and Kv2.1 and Nav1.2, Nav1.6, respectively These channels are critical in controlling neuronal intrinsic excitability and are among the best investigated VGCs (Vacher et al, 2008; Catterall, 2012; Vacher and Trimmer, 2012; Trimmer, 2015; Table 1). Principles underlying their polarized distribution and function in neurons are better understood and might be paradigmatic to understand the mechanisms controlling the subcellular distribution and function of other ion channels present in axons and dendrites

SEGREGATED DISTRIBUTION OF VGCs IN DENDRITES

Physiological functions

Nav Channels

Kv Channels

CONCLUDING REMARKS