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The kinetics of inhibition of rat recombinant heteromeric α1β glycine receptors by the low‐affinity antagonist SR‐95531
Author(s) -
Beato Marco,
Burzomato Valeria,
Sivilotti Lucia G.
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.126888
Subject(s) - glycine , glycine receptor , receptor , antagonist , kinetics , chemistry , recombinant dna , biophysics , hek 293 cells , biochemistry , biology , physics , amino acid , gene , quantum mechanics
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 α1β 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.