title: Mechanism linking NMDA receptor activation to modulation of voltage-gated sodium current in distal retina.
abstract: In this study, we investigated the mechanism that links activation of N-methyl-D-aspartate (NMDA) receptors to inhibition of voltage-gated sodium channels in isolated catfish cone horizontal cells. NMDA channels were activated in voltage-clamped cells incubated in low-calcium saline or dialyzed with the calcium chelator BAPTA to determine that calcium influx through NMDA channels is required for sodium channel modulation. To determine whether calcium influx through NMDA channels triggers calcium-induced calcium release (CICR), cells were loaded with the calcium-sensitive dye calcium green 2 and changes in relative fluorescence were measured in response to NMDA. Responses were compared with measurements obtained when caffeine depleted stores. Voltage-clamp studies demonstrated that CICR modulated sodium channels in a manner similar to that of NMDA. Blocking NMDA receptors with AP-7, blocking CICR with ruthenium red, depleting stores with caffeine, or dialyzing cells with calmodulin antagonists W-5 or peptide 290-309 all prevented sodium channel modulation. These results support the hypothesis that NMDA modulation of voltage-gated sodium channels in horizontal cells requires CICR and activation of a calmodulin-dependent signaling pathway.
authors.affiliation: Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
authors.forename: Scott F
authors.initials: SF
authors.lastname: Davis
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Linn
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000502:physiology; D004553:Electric Conductivity; D004594:Electrophysiology; D007059:Ictaluridae; D007425:Intracellular Membranes / Q000378:metabolism; D015640:Ion Channel Gating; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012160:Retina / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D002147:Calmodulin; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D002118:Calcium