Sanvido, I. | Search bioRxiv

bioRxiv2026

Inflammatory burning pain depends on a specific line of nociceptors

The development and persistence of burning pain and heat hyperalgesia following tissue injury and the subsequent inflammatory response, depend on the nuclear enzyme mitogen- and stress-activated kinase 1 (MSK1) expressed in a specific subset of transient receptor potential subfamily V member 1 (TRPV1)-expressing primary sensory neurons termed nociceptors, which are specialised for detecting harmful stimuli. Inflammation up-regulates and activates MSK1, and MSK1 governs TRPV1 expression in the MSK1 and TRPV1 co-expressing mouse and human nociceptors. Importantly, inhibition of inflammatory MSK1-mediated TRPV1 upregulation protects from heat hypersensitivity without affecting other relevant TRPV1 functions, such as the sensation of acute painful heat stimuli or the maintenance of the body core temperature. The newly discovered importance of the interaction between MSK1 and TRPV1 in a specific line of nociceptors provides mechanistic understanding of inflammatory pain and heat hyperalgesia pathogenesis.

neuroscience↗

bioRxiv2024

Versatile Functional Interaction between Electrically Silent KV Subunits and KV7 Potassium Channels

Voltage-gated K+ (KV) channels govern K+-ion flux across cell membranes in response to changes in membrane potential. They are formed by the assembly of four subunits, typically from the same family. Electrically silent KV channels (KVS), however, are unable to conduct currents on their own. It has been assumed that these KVS must obligatorily assemble with subunits from the KV2 family into heterotetrameric channels, thereby giving raise to currents distinct from those of homomeric KV2 channels. Herein, we show that KVS subunits indeed also modulate the activity, biophysical properties and surface expression of recombinant KV7 isoforms in a subunit-specific manner. Employing co-immunoprecipitation, and proximity labelling, we unveil the spatial coexistence of KVS and KV7 within a single protein complex. Electrophysiological experiments further indicate functional interaction and probably heterotetramer formation. Finally, single-cell transcriptomic analyses identify native cell types in which this KVS and KV7 interaction may occur. Our finding demonstrate that KV cross-family interaction is much more versatile than previously thought - possibly serving nature to shape potassium conductance to the needs of individual cell types.

neuroscience↗