Neuron
Volume 77, Issue 5, 6 March 2013, Pages 899-914
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Article
Kv1.1 Channels Act as Mechanical Brake in the Senses of Touch and Pain

https://doi.org/10.1016/j.neuron.2012.12.035Get rights and content
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Summary

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.

Highlights

► A mechanosensitive K+ current (IKmech) is described in mouse sensory neurons ► IKmech is carried by mechanosusceptible Kv1.1-Kv1.2 heteromeric channels ► IKmech regulates mechanical threshold for firing in mechanonociceptors ► Kv1.1 dominant-negative mice develop mechanical allodynia but not heat hyperalgesia

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