Kv1.1 channels act as mechanical brake in the senses of touch and pain.

Abstract:

:Molecular determinants of threshold sensitivity of mammalian mechanoreceptors are unknown. Here, we identify a mechanosensitive (MS) K(+) current (IKmech) that governs mechanical threshold and adaptation of distinct populations of mechanoreceptors. Toxin profiling and transgenic mouse studies indicate that IKmech is carried by Kv1.1-Kv1.2 heteromers. Mechanosensitivity is attributed to Kv1.1 subunits, through facilitation of voltage-dependent open probability. IKmech is expressed in high-threshold C-mechano-nociceptors (C-HTMRs) and Aβ-mechanoreceptors, but not in low-threshold C-mechanoreceptors. IKmech opposes depolarization induced by slow/ultraslow MS cation currents in C-HTMRs, thereby shifting mechanical threshold for firing to higher values. However, due to kinetics mismatch with rapidly-adapting MS cation currents, IKmech tunes firing adaptation but not mechanical threshold in Aβ-mechanoreceptors. Expression of Kv1.1 dominant negative or inhibition of Kv1.1/IKmech caused severe mechanical allodynia but not heat hyperalgesia. By balancing the activity of excitatory mechanotransducers, Kv1.1 acts as a mechanosensitive brake that regulates mechanical sensitivity of fibers associated with mechanical perception.

journal_name

Neuron

journal_title

Neuron

authors

Hao J,Padilla F,Dandonneau M,Lavebratt C,Lesage F,Noël J,Delmas P

doi

10.1016/j.neuron.2012.12.035

subject

Has Abstract

pub_date

2013-03-06 00:00:00

pages

899-914

issue

5

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(13)00043-3

journal_volume

77

pub_type

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