Kv1.1 Channels Act as Mechanical Brake in the Senses of Touch and Pain

Molecular determinants of threshold sensitivity of mammalian mechanoreceptors are unknown. Here, we identify a nnechanosensitive (MS) K+ current (I-Kmech) that governs mechanical threshold and adaptation of distinct populations of mechanoreceptors. Toxin profiling and transgenic mouse studies indicate that I-Kmech is carried by Kv1.1-Kv1.2 heteromers. Mechanosensitivity is attributed to Kv1.1 subunits, through facilitation of voltage-dependent open probability. I-Kmech is expressed in high-threshold C-mechano-nociceptors (C-HTMRs) and A beta-mechanoreceptors, but not in low-threshold C-mechanoreceptors. I-Kmech 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, I-Kmech tunes firing adaptation but not mechanical threshold in A beta-mechanoreceptors. Expression of Kv1.1 dominant negative or inhibition of Kv1.1/I-Kmech 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.