Contribution of Neuronal and Glial Two-Pore-Domain Potassium Channels in Health and Neurological Disorders.

Yuncheng Luo,Lu Huang,Ping Liao,Ruotian Jiang,Fang Pan

doi:10.1155/2021/8643129

Yuncheng Luo, Lu Huang + Show 3 more

Open Access

https://doi.org/10.1155/2021/8643129

Copy DOI

Abstract

Two-pore-domain potassium (K2P) channels are widespread in the nervous system and play a critical role in maintaining membrane potential in neurons and glia. They have been implicated in many stress-relevant neurological disorders, including pain, sleep disorder, epilepsy, ischemia, and depression. K2P channels give rise to leaky K+ currents, which stabilize cellular membrane potential and regulate cellular excitability. A range of natural and chemical effectors, including temperature, pressure, pH, phospholipids, and intracellular signaling molecules, substantially modulate the activity of K2P channels. In this review, we summarize the contribution of K2P channels to neuronal excitability and to potassium homeostasis in glia. We describe recently discovered functions of K2P channels in glia, such as astrocytic passive conductance and glutamate release, microglial surveillance, and myelin generation by oligodendrocytes. We also discuss the potential role of glial K2P channels in neurological disorders. In the end, we discuss current limitations in K2P channel researches and suggest directions for future studies.

Highlights

Ion channels in the cell membrane, potassium channels, play a vital role in the resting membrane potential of neurons and in the transmission of action potentials [1,2,3,4,5]
We focus on how K2P channels in neurons help maintain resting membrane potential and regulate excitability, and on how K2P channels in glia help maintain potassium homeostasis
Some K2P channels mediate nociception and pathological pain, and knocking them out in mice increases sensitivity to noxious stimuli [14, 15]. These findings indicate a strong association between K2P channels and neuronal excitability

Summary

Introduction

Ion channels in the cell membrane, potassium channels, play a vital role in the resting membrane potential of neurons and in the transmission of action potentials [1,2,3,4,5]. An appropriate resting membrane potential requires a leaky K+ current, and two-pore-domain potassium (K2P) channels appear crucial in providing such current. These channels remain open (“leaky”) across the range of physiological voltages, as well as during action potentials [6,7,8]. Glia are nonneuronal cells in the nervous system that do not produce electrical impulses Instead, they maintain homeostasis of certain ions, K+, in the extracellular environment. We focus on how K2P channels in neurons help maintain resting membrane potential and regulate excitability, and on how K2P channels in glia help maintain potassium homeostasis

K2P Channels and the Excitability of Neurons

K2P and the Potassium Homeostasis of Glia

Future Perspectives