Menthol excites dural afferent neurons by inhibiting leak K + conductance in rats.

Autor: Lee S; Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Republic of Korea., Jang IS; Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu 41940, Republic of Korea. Electronic address: jis7619@knu.ac.kr.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2023 Sep 14; Vol. 813, pp. 137427. Date of Electronic Publication: 2023 Aug 05.
DOI: 10.1016/j.neulet.2023.137427
Abstrakt: Menthol-a natural organic compound-is widely used for relieving various pain conditions including migraine. However, a high dose of menthol reportedly decreases pain thresholds and enhances pain responses. Accordingly, in the present study, we addressed the effect of menthol on the excitability of acutely isolated dural afferent neurons, which were identified with a fluorescent dye, using the whole-cell patch-clamp technique. Under a voltage-clamped condition, menthol altered the holding current levels in a concentration-dependent manner. The menthol-induced current (I Menthol ) remained unaffected by the addition of selective transient receptor potential melastatin 8 antagonists. Moreover, the reversal potential of I Menthol was similar to the equilibrium potential of K + . I Menthol was accompanied by an increase in input resistance, thereby suggesting that menthol decreases the leak K + conductance. Under a current-clamped condition, menthol caused depolarization of the membrane potential and decreased the threshold for the generation of action potential. While the I Menthol was substantially inhibited by 10 μM XE-991, a selective K V 7 blocker, the M-current mediated by K V 7 was not detected in the nociceptive neurons tested in the present study. Moreover, I Menthol decreased under acidic extracellular pH conditions or in the presence of 3 μM A-1899, a selective K2P3.1 and K2P9.1 blocker. The present results suggest that menthol inhibits leak K + channels, possibly acid-sensitive two-pore domain K + channels, thereby increasing the excitability of nociceptive sensory neurons. The resultant increase in neuron excitability may partially be responsible for the pronociceptive effect mediated by high menthol doses.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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