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,I-I.) in concentration-dependent manner. An amount of 1 mM salicylate shifted the steady-state inactivation curve Of INa negatively by about 5 mV, shifted the steady-state activation and inactivation curve of I-K(DR) negatively by approximately 14 mV and 17 mV, respectively, and shifted the steady-state activation curve of I-CA,I-I. negatively by about 10 mV. 1 mM 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. (c) 2007 Elsevier Ltd. All rights reserved.NeurosciencesPharmacology & PharmacySCI(E)0ARTICLE7870-8805