Role of Elkin1 in pain-sensing nerves

Mechanosensation is a process by which nerves encode physical stimuli such as cotton swab or pinprick into electrical signals that can be understood by the nervous system. But what is the molecular basis of mechanosensation, allowing this process to occur? New evidence suggests Elkin1 is an ion channel required for light touch sensation in mice and humans. Here, we explore its function in nociceptor physiology.Our results show that Elkin1-/- knockouts exhibit lowered mechanical sensitivity when tested in behavioral assays using a hindpaw stimulation. Electron microscopy showed no structural changes in the somatosensory system of mutant animals, therefore we next investigated physiology of sensory afferents. Cutaneous mechanoreceptors were studied with the use of ex vivo mice skin-nerve preparation, with main focus on c-fibers; small diameter unmyelinated sensory fibers mainly involved in sensing mechanical pain. Extracellular recordings from single nerve fibers, made during simultaneous mechanical stimulation of receptors located in the skin, showed a changed pattern of activity in response to mechanical stimulation with faster adaptation in Elkin1-/- animals.Furthermore, we explore the relationship of Elkin1 with Piezo2, a bona fide mechanosensitive channel. Again, using behavioral and electrophysiological methods, we investigated double knockout animals to check for possible functional interaction between Elkin1 and Piezo2.Summarizing, we show changes in functioning of the pain-sensing nerves of Elkin1-/- knockout mice and propose Elkin1 as a novel mechanosensory protein required for both light touch and pain sensation.