The kinetics of inhibition of rat recombinant heteromeric alpha1beta glycine receptors by the low-affinity antagonist SR-95531

The GABA(A) antagonist SR-95531 (gabazine) is known to block glycine receptors, albeit with low affinity. We have studied the effect of SR-95531 on rat recombinant alpha1beta glycine receptors expressed in human embryonic kidney (HEK293) cells by recording macroscopic currents elicited by rapid glyc...

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Bibliographic Details
Published inThe Journal of physiology Vol. 580; no. Pt 1; pp. 171 - 179
Main Authors Beato, Marco, Burzomato, Valeria, Sivilotti, Lucia G
Format Journal Article
LanguageEnglish
Published England 01.04.2007
Subjects
Animals
Cell Line
Electrophysiology
Glycine - metabolism
Glycine - pharmacology
Glycine Agents - pharmacology
Humans
Kinetics
Models, Statistical
Patch-Clamp Techniques
Pyridazines - pharmacology
Rats
Receptors, Glycine - antagonists & inhibitors
Recombinant Proteins
Synapses - drug effects
Synapses - metabolism
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Summary:The GABA(A) antagonist SR-95531 (gabazine) is known to block glycine receptors, albeit with low affinity. We have studied the effect of SR-95531 on rat recombinant alpha1beta glycine receptors expressed in human embryonic kidney (HEK293) cells by recording macroscopic currents elicited by rapid glycine application to outside-out patches. SR-95531 has a fast unbinding rate (k(offSR), about 3000 s(-1)) and this means that the time course of its unbinding is comparable to the expected time course of the transmitter in the cleft. We also found that equilibrium applications of SR-95531 reduced the response to brief glycine applications by an amount inversely proportional to the duration of glycine application. The fast unbinding rate of SR-95531 from the glycine receptor will make it useful for establishing the time course of glycine concentration at glycinergic synapses.
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ISSN:0022-3751
1469-7793