TREK-1 and TRAAK Are Principal K+ Channels at the Nodes of Ranvier for Rapid Action Potential Conduction on Mammalian Myelinated Afferent Nerves

Neuron. 2019 Dec 4;104(5):960-971.e7. doi: 10.1016/j.neuron.2019.08.042. Epub 2019 Oct 17.

Abstract

Rapid conduction of nerve impulses is critical in life and relies on action potential (AP) leaps through the nodes of Ranvier (NRs) along myelinated nerves. While NRs are the only sites where APs can be regenerated during nerve conduction on myelinated nerves, ion channel mechanisms underlying the regeneration and conduction of APs at mammalian NRs remain incompletely understood. Here, we show that TREK-1 and TRAAK, the thermosensitive and mechanosensitive two-pore-domain potassium (K2P) channels, are clustered at NRs of rat trigeminal Aβ-afferent nerves with a density over 3,000-fold higher than that on their somas. These K2P channels, but not voltage-gated K+ channels as in other parts of nerves, are required for rapid AP repolarization at the NRs. Furthermore, these channels permit high-speed and high-frequency AP conduction along the myelinated afferent nerves, and loss of function of these channels at NRs retards nerve conduction and impairs sensory behavioral responses in animals.

Keywords: action potential; conduction velocity; leak K(+) currents; myelinated nerve; node of Ranvier; saltatory conduction; sensory; temperature; two-pore-domain K(+) channels.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Male
  • Nerve Fibers, Myelinated / metabolism
  • Neural Conduction / physiology*
  • Neurons, Afferent / metabolism
  • Potassium Channels / metabolism*
  • Potassium Channels, Tandem Pore Domain / metabolism*
  • Ranvier's Nodes / metabolism*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Kcnk4 protein, rat
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • potassium channel protein TREK-1