PT  - JOURNAL ARTICLE
AU  - Stephen G. Brohawn
AU  - Weiwei Wang
AU  - Jürgen R. Schwarz
AU  - Annie Handler
AU  - Ernest B. Campbell
AU  - Roderick MacKinnon
TI  - The mechanosensitive ion channel TRAAK is localized to the mammalian node of Ranvier
AID  - 10.1101/713990
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 713990
4099  - http://biorxiv.org/content/early/2019/07/25/713990.short
4100  - http://biorxiv.org/content/early/2019/07/25/713990.full
AB  - 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 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. Mechanical gating in TRAAK might serve a neuroprotective role by counteracting mechanically-induced ectopic action potentials. Alternatively, TRAAK may open in response to mechanical forces in the nodal membrane associated with depolarization during saltatory conduction and thereby contribute to repolarization of the node for subsequent spikes.