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Inhibition of acid‐sensing ion channels by levo‐tetrahydropalmatine in rat dorsal root ganglion neurons
Author(s) -
Liu TingTing,
Qu ZuWei,
Qiu ChunYu,
Qiu Fang,
Ren Cuixia,
Gan Xiong,
Peng Fang,
Hu WangPing
Publication year - 2015
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23484
Subject(s) - acid sensing ion channel , dorsal root ganglion , extracellular , pharmacology , depolarization , chemistry , tetrahydropalmatine , nociceptor , analgesic , ion channel , nociception , corydalis , electrophysiology , biophysics , neuroscience , medicine , biochemistry , sensory system , biology , receptor , traditional chinese medicine , alternative medicine , pathology
Levo‐tetrahydropalmatine ( l ‐THP), a main bioactive Chinese herbal constituent from the genera Stephania and Corydalis , has been in use in clinical practice for years in China as a traditional analgesic agent. However, the mechanism underlying the analgesic action of l ‐THP is poorly understood. This study shows that l ‐THP can exert an inhibitory effect on the functional activity of native acid‐sensing ion channels (ASICs), which are believed to mediate pain caused by extracellular acidification. l ‐THP dose dependently decreased the amplitude of proton‐gated currents mediated by ASICs in rat dorsal root ganglion (DRG) neurons. l ‐THP shifted the proton concentration–response curve downward, with a decrease of 40.93% ± 8.45% in the maximum current response to protons, with no significant change in the pH 0.5 value. Moreover, l ‐THP can alter the membrane excitability of rat DRG neurons to acid stimuli. It significantly decreased the number of action potentials and the amplitude of the depolarization induced by an extracellular pH drop. Finally, peripherally administered l ‐THP inhibited the nociceptive response to intraplantar injection of acetic acid in rats. These results indicate that l ‐THP can inhibit the functional activity of ASICs in dissociated primary sensory neurons and relieve acidosis‐evoked pain in vivo, which for the first time provides a novel peripheral mechanism underlying the analgesic action of l ‐THP. © 2014 Wiley Periodicals, Inc.