【摘 要】
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Citalopram, a selective serotonin reuptake inhibitor (SSRI), as well as an antidepressant, is thought to exert its effects by increasing synaptic serotonin (5-HT) levels.However, few studies have addr
【机 构】
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Institutes of Brain Science, School of Life Sciences and State Key Laboratory of Medical Neurobiolog
【出 处】
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中国神经科学学会第九届全国学术会议暨第五届会员代表大会
论文部分内容阅读
Citalopram, a selective serotonin reuptake inhibitor (SSRI), as well as an antidepressant, is thought to exert its effects by increasing synaptic serotonin (5-HT) levels.However, few studies have addressed the possibility that citalopram has other molecular mechanisms of action.We examined the effects of citalopram on delayed rectifier outward K+ current (IK) in mouse cortical neurons.Extracellular citalopram reversibly inhibited IK in a dose-dependent manner and significantly shifted both steady-state activation and inactivation curves towards hyperpolarization direction.Neither 5-HT itself nor antagonists of 5-HT and dopamine receptors could abolish citalopram-induced inhibition of IK.In addition, intracellular application of GTPγ-S similarly failed to prevent the inhibition of IK by citalopram.When applied intracellularly, citalopram had no effect on IK and also did not influence the reduction of IK induced by extracellular citalopram.The effect of citalopram was use-dependent, but not frequency-dependent, and did not require channel opening.Electrophysiological recordings in acute prepared cortical slice showed that citalopram significantly reduced the action potential (AP) firing frequency of cortical neurons and increased action potential duration (APD).The selective Kv2.1 subunit blocker Jingzhaotoxin-Ⅲ (JZTX-Ⅲ) did not abolish citalopram-induced IK inhibition.Transfection of HEK293 cells with Kv2.1 or Kv2.2 constructs indicated that citalopram mainly inhibited Kv2.2 current.Taken together, we suggest that citalopram-induced inhibition of IK in mouse cortical neurons is independent of G-protein coupled receptors, and might exert its antidepressant effects by enhancing presynaptic efficiency.Our results may help to explain some of the unknown therapeutic effects on antidepressant of citalopram.
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