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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.

journal_name

Neurosci Res

journal_title

Neuroscience research

authors

Koike M,Iino M,Ozawa S

doi

10.1016/s0168-0102(97)00067-9

subject

Has Abstract

pub_date

1997-09-01 00:00:00

pages

27-36

issue

1

eissn

0168-0102

issn

1872-8111

pii

S0168-0102(97)00067-9

journal_volume

29

pub_type

杂志文章

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