title: Blocking effect of 1-naphthyl acetyl spermine on Ca(2+)-permeable AMPA receptors in cultured rat hippocampal neurons.
abstract: Effects of 1-naphthyl acetyl spermine (NASPM), a synthetic analogue of Joro spider toxin (JSTX), on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors were studied in cultured rat hippocampal neurons using the whole-cell patch clamp technique. A population of cultured neurons had AMPA receptors with a strong inward rectification and a high permeability to Ca2+ (type II neurons). Whereas most neurons (type I neurons) had AMPA receptors with a slight outward rectification and little Ca2+ permeability. NASPM selectively suppressed the inwardly rectifying and Ca(2+)-permeable AMPA receptors expressed in type II neurons. It had no effect on AMPA receptors in type I neurons. The blocking effect of NASPM on the Ca(2+)-permeable AMPA receptors was use and voltage-dependent. When the effect of NASPM reached a steady state, current responses induced by ionophoretic applications of kainate, a non-desensitizing agonist of AMPA receptors, in type II neurons were suppressed by NASPM in a dose-dependent manner at -60 mV (IC50 0.33 microM, and Hill coefficient 0.94). The response to kainate recovered partially after washing out NASPM. NASPM did not affect the Ca(2+)-permeable AMPA receptors when the neuronal membrane was held at potentials more positive than +40 mV. Furthermore, the blockade by NASPM which was attained at negative potentials was transiently removed by shifting membrane potential to +60 mV for 5 s together with a single ionophoretic application of kainate. NASPM would be useful as a pharmacological tool for elucidating both physiological and pathological significances of Ca(2+)-permeable AMPA receptors in the CNS.
authors.affiliation: Department of Physiology, Gunma University School of Medicine, Japan. mkoike@sb.gunma.u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Koike
authors.forename: M
authors.initials: M
authors.lastname: Iino
authors.forename: S
authors.initials: S
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D018091:Receptors, AMPA / Q000187:drug effects*; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013111:Spider Venoms / Q000494:pharmacology
chemical_list: C044936:JSTX spider toxin; D009498:Neurotoxins; D018091:Receptors, AMPA; D013111:Spider Venoms; C067506:1-naphthylacetylspermine; D013096:Spermine; D002118:Calcium