TRESK background potassium channel modifies the TRPV1-mediated nociceptor excitability in sensory neurons.

Abstract

TWIK-related spinal cord potassium channel (TRESK) background potassium channels have a key role in controlling resting membrane potential and excitability of sensory neurons. A frameshift mutation leading to complete loss of TRESK function has been identified in members of a family suffering from migraine with aura. In the present study, we examined the role of TRESK channels on nociceptor function in mice. Calcium imaging was used to investigate the role of TRESK channels in the modulation of the response evoked by transient receptor potential vanilloid 1 (TRPV1) receptor stimulation in dorsal root ganglion neurons. Release of calcitonin gene-related peptide from trigeminal afferents and changes in meningeal blood flow were also measured. Experiments were performed on wild-type and TRESK knockout animals. Inhibition of TRESK increased the TRPV1-mediated calcium signal in dorsal root ganglion neurons and potentiated capsaicin-induced increases in calcitonin gene-related peptide release and meningeal blood flow. Activation of TRESK decreased the capsaicin sensitivity of sensory neurons, leading to an attenuation of capsaicin-induced increase in meningeal blood flow. In TRESK knockout animals, TRPV1-mediated nociceptive reactions were unaffected by pretreatment with TRESK modulators. Pharmacological manipulation of TRESK channels influences the TRPV1-mediated functions of nociceptors. Altered TRESK function might contribute to trigeminal nociceptor sensitization in migraine patients.