Axonal membrane stretch suppresses neuronal excitability by activating mechanosensitive K2P channels at the node of Ranvier

Molecular Brain

Micro Report

Koichi Noguchi¹  Hirosato Kanda²  Yi Dai³ 

[1] Laboratory of Basic Pain Research, Hyogo Medical University, 650-8530, Kobe, Hyogo, Japan;School of Pharmacy, Hyogo Medical University, 650-8530, Kobe, Hyogo, Japan;Laboratory of Basic Pain Research, Hyogo Medical University, 650-8530, Kobe, Hyogo, Japan;School of Pharmacy, Hyogo Medical University, 650-8530, Kobe, Hyogo, Japan;Laboratory of Basic Pain Research, Hyogo Medical University, 650-8530, Kobe, Hyogo, Japan;Department of Anatomy and Neuroscience, Hyogo Medical University, 663-8501, Nishinomiya, Hyogo, Japan;

关键词: Node of Ranvier;    Two-pore-domain potassium channels;    Membrane stretch;    Action potential;    Single-channel activity;   

DOI  :  10.1186/s13041-023-01000-6

 received in 2022-11-15, accepted in 2023-01-10,  发布年份 2023

来源: Springer

【 摘 要 】

Saltatory conduction is the propagation of action potentials along myelinated nerves, which enables fast propagation through the node of Ranvier. Recently, we demonstrated that K2P channels, TWIK-related K+ channel-1 (TREK-1), and TWIK-related arachidonic acid-activated K + channel (TRAAK), are highly expressed in the mammalian node of Ranvier of sensory nerves and have an important role in action potential repolarization instead of voltage-gated K+ channels. TREK-1/TRAAK channels are activated by membrane depolarization as well as various stimuli, such as temperature, pH, arachidonic acid, and mechanical membrane stretch. Although membrane mechanical stretch has been suggested to modulate action potential conduction, how membrane stretching modulates intrinsic electrophysiological properties at the node of Ranvier remains unclear. In the present study, we examined the effects of membrane stretch on neuronal membranes at the node of Ranvier in rat sciatic nerves. The single-channel conductance was approximately 90 pS at 80 mV. Membrane stretch increased the single-channel event numbers and open probability in a pressure-dependent manner. Consistent with single-channel activity, intra-pipette positive pressure increased outward leak currents and decreased membrane excitability in a whole-cell configuration. Furthermore, blockage of TREK-1/TRAAK channels by Ba2+ reversed the changes in the intrinsic electrophysiological properties induced by intra-pipette pressure. These results indicate that the activation of mechanosensitive TREK-1/TRAAK channels may suppress neuronal excitability following axonal stretch. Our findings suggest that TREK-1/TRAAK channels may play an important role in the prevention of ectopic action potential discharge at the axon by intense mechanical nerve stretch under physiological conditions.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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