水杨酸钠对大鼠下丘神经元钾通道的抑制作用

目的了解瞬时外向钾通道和延迟整流钾通道在水杨酸钠导致耳鸣的机制中所起的作用。方法利用全细胞膜片钳技术研究水杨酸钠对急性分离的大鼠下丘神经元瞬时外向钾通道和延迟整流钾通道的影响。结果水杨酸钠能够抑制瞬时外向钾通道电流（IK（A））和延迟整流钾通道电流（IK（DR））的幅度，而且此抑制作用具有浓度依赖性（0．1～10mmol／L）。水杨酸钠抑制IK（A）和，IK（DR）的50％抑制浓度（IC50）值分别为2．27mmol／L和0．80mmol／L。1mmol／L水杨酸钠不改变，IK（A）的稳态激活曲线和稳态失活曲线的动力学特征，却将IK（DR）的稳态激活曲线和稳态失活曲线分别向超极化方向显著移动11mV和24mV。结论水杨酸钠以浓度依赖的方式抑制IK（A）和IK（DR），但是只影响IK（DR）的稳态激活和失活动力学特征。水杨酸钠对IK（A）和IK（DR）的影响，尤其对IK（DR）的影响可能与水杨酸钠导致耳鸣的机制有关。

Inhibition of salicylate on potassium channels in rat inferior colliculus neurons

Objective To understand what role of the transient outward potassium channels and the delayed rectifier potassium channels play in the mechanism of salicylate-induced tinnitus. Methods The effects of salicylate on the transient outward potassium channels and the delayed rectifier potassium channels in freshly dissociated inferior colliculus neurons of rats were studied, using the whole-cell voltage clamp method. Results Salicylate blocked the transient outward potassium current (I_ K(A)) and the delayed rectifier potassium current (I_ K(DR)) in concentration-dependent manner (0.1-1 mmol/L). The IC_ 50 values for the blocking action of salicylate on I_ K(A) and I_ K(DR) were 2.27 and 0.80 mmol/L, respectively. At a concentration of 1 mmol/L, salicylate did not shift the activation and inactivation curves of I_ K(A), but significantly shifted the activation and inactivation curves of I_ K(DR) negatively by approximately 11 mV and 24 mV. Conclusions Salicylate inhibits both I_ K(A) and I_ K(DR) in rat inferior colliculus neurons but only significantly affects the activation and inactivation kinetics of I_ K(DR). Effects of I_ K(A) and I_ K(DR), especially I_ K(DR), by salicylate may play an important role in salicylate-induced tinnitus.