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International Journal of Physiology and Pathophysiology

Publicou 4 edições por ano

ISSN Imprimir: 2155-014X

ISSN On-line: 2155-0158

SJR: 0.116

Amino Acid Residues Involved in Positive Modulation of α1 Glycine Receptors by Ginkgolic Acid

Volume 8, Edição 4, 2017, pp. 337-345
DOI: 10.1615/IntJPhysPathophys.v8.i4.60
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RESUMO

Previously, we have shown that ginkgolic acid has an ability to potentiate currents, mediated by α1 subunits of glycine receptor. In order to define the mechanism of the specific action of ginkgolic acid on α1 glycine receptors we have performed a comparative analysis of the amino acid sequences of α1 and α2 subunits of glycine receptor. Amino acids that contribute to the difference in interaction of ginkgolic acid with these subunits of glycine receptors were determined. Using whole-cell patch-clamp technique, we have demonstrated that mutation of three residues (T59/A26/A303) in α2 subunit for corresponding ones from α1 subunit makes α2 receptors sensitive to the potentiation by ginkgolic acid. Currents mediated by α2 mutant receptors increased by 89% ± 14 after application of ginkgolic acid. Similarly to α1 receptors, α2 mutant receptors have shown a decrease in EC50 for glycine under the action of ginkgolic acid. Thus, subunit selectivity of ginkgolic acid is strongly related to three amino acid residues that are different in α1 and α2 subunits of a glycine receptor.

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