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

Abstract

A Ca 2+-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 Ca 2+ 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, Ca 2+-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.