Inhibition of voltage-gated channel currents in rat auditory cortex neurons by salicylate.
Salicylate is a medicine for anti-inflammation with a side effect of tinnitus. To understand the mechanisms of tinnitus induced by salicylate, we studied the effects of salicylate on voltage-gated ion channels and action potential firing rates in freshly dissociated rat pyramidal neurons in auditory cortex (AC) using the whole-cell patch technique. We found that salicylate reduced the voltage-gated sodium current (I(Na)), the delayed rectifier potassium current (I(K(DR))) and the L-type voltage-gated calcium current (I(Ca,L)) in concentration-dependent manner. An amount of 1mM salicylate shifted the steady-state inactivation curve of I(Na) negatively by about 5mV, shifted the steady-state activation and inactivation curve of I(K(DR)) negatively by approximately 14mV and 17mV, respectively, and shifted the steady-state activation curve of I(Ca,L) negatively by about 10mV. 1mM salicylate significantly increased the action potential firing rates, ultimately. From the results, we speculated that through affecting the voltage-gated ion channels in AC, an important position in auditory system, salicylate increased the firing rate of neurons and enhanced neuronal excitability on the one hand, increased the excitatory transmitters release and reduced the inhibitory transmitter release on the other hand, thus finally induced tinnitus.
Liu
Yanxing
Y
Department of Pharmacology and Neurobiology, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang 050017, Hebei Province, PR China. liuyanxing75@sohu.com
Zhang
Hailin
H
Li
Xuepei
X
Wang
Yongli
Y
Lu
Hong
H
Qi
Xiang
X
Ma
Changsheng
C
Liu
Junxiu
J
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001303:Auditory Cortex / Q000166:cytology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D049990:Membrane Transport Modulators / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D012459:Salicylates / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D007473:Ion Channels; D049990:Membrane Transport Modulators; D012459:Salicylates