The Effects Of Salicylate On Voltage-gated Ion Channels In Rat Hippocampus

Tinnitus is a common hearing disorder characterized by a "phantomsensation" of ringing or buzzing in one's ear in the absence of an externalsound source. Clinical doctors have noticed the relationship between tinnitusand the emotions state. In recent years, lots of studies have found that some ofthe nuclei of the limbic system is involved in the formation of the bad mood intinnitus, such as the hippocampus. It is well known that salicylate overdose isa frequent cause of tinnitus. Thus, salicylate is widely used for studying themechanisms of tinnitus. The aim of the present study was to investigate theeffects of salicylate on voltage-gated potassium, sodium and calcium channelsin the hippocampus neurons by use of the whole-cell patch clamp method, inorder to obtain insight into the relations of the bad mood in tinnitus andvoltage-gated channels.1. Effects of salicylate on voltage-gated potassium channels in rathippocampus neuronsObjective and Methods: The aim of the present study was to obtaininsight into the effects of salicylate on electrophysiological characteristics ofthe transient outward potassium channels and the delayed rectifier potassiumchannels in hippocampus neurons. We observed the changes of the I-V curve,steady-state activation curve, steady-state inactivation curve of IK(A)and IK(DR),before and after1mM salicylate application.Results: The results showed salicylate inhibited IK(A)and IK(DR)inhippocampus neurons in concentration-dependent manner. The steady-stateactivation curve and steady-state inactivation curve of IK(A)were not shiftedalong the voltage axis with1mM salicylate application. So far as IK(DR), with1mM salicylate application, its steady-state activation curve was shifted byabout12mV in the hyperpolarizing direction, and its steady-state inactivation curve was shifted by about19mV in the hyperpolarizing direction.Conclusion: Through its inhibition on IK(A)and IK(DR)in hippocampusneurons, salicylate prolonged the time of AP, promoted neurotransmitterrelease, increased the neuronal firing rate, and finally enhanced neuronalexcitability.1. Effects of salicylate on voltage-gated sodium channels in rathippocampus neurons.Objective and Methods: The aim of the present study was to obtaininsight into the effects of salicylate on electrophysiological characteristics ofthe voltage-gated sodium channels in hippocampus neurons. We observed thechanges of the I-V curve, steady-state activation curve, steady-stateinactivation curve of INa, before and after1mM salicylate application.Results: The results showed salicylate inhibited the INain hippocampusneurons in concentration-dependent manner. With1mM salicylate application,its steady-state activation curve was shifted by about10mV in thehyperpolarizing direction, and its steady-state inactivation curve was notshifted along voltage axis.Conclusion: Through its action on INain hippocampus neurons,salicylate decreased the current amplitude, reduced the threshold of AP,enhanced the excitability of the neurons, increased the neuronal firing rate,and promoted neurotransmitter release.3. Effects of salicylate on voltage-gated calcium channels in rathippocampus neurons.Objective and Methods: The aim of the present study was to obtaininsight into the effects of salicylate on electrophysiological characteristics ofthe voltage-gated calcium channels in hippocampus neurons. We observed thechanges of the I-V curve, steady-state activation curve, steady-stateinactivation curve of ICa, before and after1mM salicylate application.Results: The results showed salicylate inhibited ICain hippocampusneurons in concentration-dependent manner. With1mM salicylate application,its steady-state activation curve was shifted by about9mV in the hyperpolarizing direction, and its steady-state inactivation curve was notshifted along voltage axis.Conclusion: Through its inhibition on ICain hippocampus neurons,salicylate decreased the release of neurotransmitters in hippocampus neurons.It may be the main reason which decreased the release of inhibitoryneurotransmitters,and the decrease of inhibitory neurotransmitters mightresulte in overexcitation of neurons.Summary: The inhibition of salicylate on IK(DR)(IC501.43mM)>theinhibition of it on ICa(IC50=1.64mM)>the inhibition of it on INa(IC50=2.07)> the inhibition of it on IK(A)(IC50=2.18mM). Salicylate changed thesteady-state activation curve and steady-state inactivation curve of IK(DR),made them move to the hyperpolarizing direction; while it also changed thesteady-state activation curve of INAand ICa, made it move to thehyperpolarizing direction; but it had no affections on IK(A).