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

Background: 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.

Methods: 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.

Results: 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.

Conclusions: Pharmacological manipulation of TRESK channels influences the TRPV1-mediated functions of nociceptors. Altered TRESK function might contribute to trigeminal nociceptor sensitization in migraine patients.