The mechanosensitive ion channel TRAAK is localized to the mammalian node of Ranvier.

Stephen G Brohawn,Annie Handler,Roderick Mackinnon,Ernest B Campbell,Jürgen R Schwarz,Weiwei Wang

doi:10.7554/elife.50403

Stephen G Brohawn, Annie Handler + Show 4 more

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https://doi.org/10.7554/elife.50403

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Abstract

TRAAK is a membrane tension-activated K+ channel that has been associated through behavioral studies to mechanical nociception. We used specific monoclonal antibodies in mice to show that TRAAK is localized exclusively to nodes of Ranvier, the action potential propagating elements of myelinated nerve fibers. Approximately 80 percent of myelinated nerve fibers throughout the central and peripheral nervous system contain TRAAK in what is likely an all-nodes or no-nodes per axon fashion. TRAAK is not observed at the axon initial segment where action potentials are first generated. We used polyclonal antibodies, the TRAAK inhibitor RU2 and node clamp amplifiers to demonstrate the presence and functional properties of TRAAK in rat nerve fibers. TRAAK contributes to the 'leak' K+ current in mammalian nerve fiber conduction by hyperpolarizing the resting membrane potential, thereby increasing Na+ channel availability for action potential propagation. We speculate on why nodes of Ranvier contain a mechanosensitive K+ channel.

Highlights

Mechanosensation encompasses the processes by which cells sense physical forces and transduce them into biological responses
In this study we show that the mechanosensitive TRAAK channel is localized to nodes of Ranvier in myelinated axons throughout the mammalian nervous system
Our previous X-ray crystallographic studies of H. sapiens TRAAK utilized antigen binding fragments (Fabs) of a mouse monoclonal antibody raised against the channel to facilitate crystal packing

Summary

Introduction

Mechanosensation encompasses the processes by which cells sense physical forces and transduce them into biological responses. Force-gated or mechanosensitive ion channels are cells’ fastest force sensors and are gated open by mechanical force to transduce physical stimuli into cellular electrical signals (Ranade et al, 2015). Mechanosensitive ion channels underlie less conspicuous force sensations such as proprioception, blood pressure regulation and osmolarity control (Teng et al, 2015). The prevalence of mechanically-activated currents in cells has become increasingly clear; most cell types express mechanosensitive channels including stem cells, cancer cells and neurons of the central nervous system, suggesting, perhaps, that force sensation by ion channels may be involved in more aspects of physiology than previously appreciated (Ranade et al, 2015; Teng et al, 2015; Anishkin et al, 2014).

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