A single amino acid determines the subunit-specific spider toxin block of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor channels.
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- M Blaschke
- Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Germany.
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- B U Keller
- Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Germany.
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- R Rivosecchi
- Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Germany.
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- M Hollmann
- Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Germany.
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- S Heinemann
- Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Germany.
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- A Konnerth
- Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Germany.
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説明
<jats:p>Joro spider toxin (JSTX) is one of the most potent antagonists of glutamatergic AMPA/KA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate) receptor channels in invertebrates and vertebrates. A differential blocking effect on certain types of glutamatergic synapses--e.g., parallel and climbing fiber synaptic inputs to rat cerebellar Purkinje neurons--has been shown by using a synthetic analog of the spider toxin. By investigating the molecular basis of the JSTX action on the recombinant AMPA/KA receptors GluR1-GluR4 and GluR6 expressed in Xenopus oocytes, we found that submicromolar concentrations of JSTX exert a subunit-specific block. Thus, receptor subunits forming a receptor channel with a linear current-voltage (I-V) relationship (GluR1/2, GluR2/3, and GluR6) were not affected, while receptor subunits with rectifying I-V relationships (GluR1, GluR3, GluR4, and GluR1/3) were reversibly blocked by JSTX. By using receptor-subunit mutants obtained by site-directed mutagenesis, we have identified a single amino acid position (glutamine in the proposed second transmembrane domain) that is critical for the JSTX block. Since this site has previously been shown to control the I-V relationship of the AMPA/KA receptor channel and to participate in the regulation of the channel's permeability for calcium ions, our findings suggest that JSTX binds close to the central pore region of the channel.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 90 (14), 6528-6532, 1993-07-15
Proceedings of the National Academy of Sciences
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詳細情報 詳細情報について
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- CRID
- 1363388843873109888
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- NII論文ID
- 30016294516
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- ISSN
- 10916490
- 00278424
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