title: 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 (100-200microM) 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.
authors.affiliation: Department of Neuroscience, Nobel Institute for Neurophysiology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.forename: Sten
authors.initials: S
authors.lastname: Grillner
authors.forename: Peter
authors.initials: P
authors.lastname: Wallén
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001030:Apamin / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D005439:Flufenamic Acid / Q000494:pharmacology*; D017629:Gap Junctions / Q000187:drug effects; D066298:In Vitro Techniques; D007798:Lampreys / Q000502:physiology*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015220:Calcium Channels; D002614:Chelating Agents; D018690:Excitatory Amino Acid Agonists; D026902:Potassium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D001030:Apamin; D004533:Egtazic Acid; D005439:Flufenamic Acid; D016202:N-Methylaspartate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid