Effects of flufenamic acid on fictive locomotion, plateau potentials, calcium channels and NMDA receptors in the lamprey spinal cord

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• 作者：Di Wang ; Sten Grillner and Peter Wallé ; n
• 关键词：I_CAN ; Network ; Central pattern generator ; Membrane potential oscillations ; NMDA
• 刊名：Neuropharmacology
• 出版年：2006
• 期刊代码：33_00283908
• 类别：pha
• 出版时间：November 2006
• 卷：51
• 期：6
• 页码：1038-1046
• 文件大小：664 K

摘要

A Ca²⁺-activated, non-selective cation current (I_CAN) has been suggested to contribute to plateau potentials in lamprey reticulospinal neurons, providing the drive for locomotor initiation. Flufenamic acid (FFA) is commonly used as a blocker of I_CAN. To explore the effects of FFA on spinal locomotor pattern generation, we induced fictive locomotion in the isolated lamprey spinal cord. Bath-applied FFA (100–200 μM) caused a marked reduction of amplitude and regularity of the locomotor burst activity. We next analyzed the NMDA-induced membrane potential oscillations in single spinal neurons. The duration of depolarizing plateaus was markedly reduced when applying FFA, suggesting an involvement of I_CAN. However, in experiments with intracellular injection of the Ca²⁺ chelator BAPTA, and in the presence of the K_Ca-channel blocker apamin, no support was found for an involvement of I_CAN. We therefore explored alternative explanations of the effects of FFA. FFA reduced the size of the slow, Ca²⁺-dependent afterhyperpolarization, suggesting an influence on calcium channels. FFA also reduced the NMDA component of reticulospinal EPSPs as well as NMDA-induced depolarizing responses, demonstrating an influence on NMDA receptors. These non-selective effects of FFA can account for its influence on fictive locomotion and on membrane potential oscillations and thus, a specific involvement of the I_CAN current in the lamprey spinal cord is not supported.