Effects of salicylate on voltage-gated sodium channels in rat inferior colliculus neurons.
To investigate the effects of the tinnitus inducer, sodium salicylate, on voltage-gated sodium channels, we studied freshly dissociated inferior colliculus neurons of rats by the whole-cell voltage clamp method. Salicylate blocked sodium channels in concentration-dependent manner (0.1-10 mM), and the IC50 value of salicylate was estimated to be 1.43 mM after application. The sodium conductance-voltage curve did not shift along the voltage axis with salicylate application. In contrast, the steady-state sodium channel inactivation curve was shifted by about 9 mV in the hyperpolarizing direction. In addition, salicylate delayed the sodium channel recovery from inactivation by increasing the slow time constant. It was concluded that salicylate bound to the resting and inactivated sodium channels to cause blocking, with a higher affinity for the latter state. Our results suggest that salicylate causes a concentration-dependent blockade of voltage-gated sodium channels and shifts the inactivation curve to more hyperpolarized potentials, which could be related to the mechanism of salicylate-induced tinnitus.
Liu
Yanxing
Y
Department of Otorhinolaryngology, Peking University Third Hospital, 49# Huayuan Road, Haidian District, Beijing 100083, PR China. liuyanxiang75@sohu.com
Li
Xuepei
X
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D007245:Inferior Colliculi / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D015640:Ion Channel Gating; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism*; D012980:Sodium Salicylate / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012980:Sodium Salicylate