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TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity
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Background potassium-permeable ion channels play a critical role in tuning the excitability of nociceptors, yet the precise role played by different subsets of channels is not fully understood. Decreases in TRESK (TWIK-related spinal cord K+ channel) expression/function enhance sensory neurons excitability, but its role in somatosensory perception and nociception is poorly understood. Here, we used a TRESK knockout (KO) mouse to address these questions. We show that TRESK regulates the sensitivity of sensory neurons in a modality-specific manner, contributing to mechanical and cold sensitivity but without any effect on heat sensitivity. Nociceptive neurons isolated from TRESK KO mice show a decreased threshold for activation and skin nociceptive C-fibers show an enhanced activation by cold and mechanical stimulation that was also observed in behavioral tests in vivo. TRESK is also involved in osmotic pain and in early phases of formalin-induced inflammatory pain, but not in the development of mechanical and heat hyperalgesia during chronic pain. In contrast, mice lacking TRESK present cold allodynia that is not further enhanced by oxaliplatin. In summary, genetic removal of TRESK uncovers enhanced mechanical and cold sensitivity, indicating that the channel regulates the excitability of specific neuronal subpopulations involved in mechanosensitivity and cold-sensing, acting as a brake to prevent activation by innocuous stimuli.
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CASTELLANOS, Aida, PUJOL COMA, Anna, ANDRES, Alba, NEGM, Ahmed, CALLEJO, Gerard, SOTO DEL CERRO, David, NOEL, Jacques, COMES I BELTRÁN, Núria, GASULL CASANOVA, Xavier. TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity. _Journal of Physiology_. 2020. Vol. 598, núm. 5, pàgs. 1017-1038. [consulta: 26 de gener de 2026]. ISSN: 0022-3751. [Disponible a: https://hdl.handle.net/2445/183514]