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First published online on January 11, 2007.
 Copyright © 2007 by The Physiological Society
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jphysiol.2006.126888v1
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Received December 18, 2006
Revised January 3, 2007
Accepted after revision January 8, 2007

The kinetics of inhibition of rat recombinant heteromeric {alpha}1{beta} glycine receptors by the low affinity antagonist SR-95531

Marco Beato1*, Valeria Burzomato1, and Lucia G Sivilotti2

1 University College London
2 UCL

* To whom correspondence should be addressed. E-mail: m.beato{at}ucl.ac.uk.

The GABAA antagonist SR-95531 (gabazine) is known to block glycine receptors, albeit with low affinity (about 200 µM). We have studied the effect of SR-95531 on rat recombinant {alpha}1{beta} glycine receptors expressed in Human Embryonic Kidney cells by recording macroscopic currents elicited by rapid glycine application to outside-out patches. SR-95531 has a fast unbinding rate (koffSR was about 3000 s-1).and this means that the time course of its unbinding is comparable to the expected time course of 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 glycine receptor will make it useful in establishing the time course of glycine concentration at glycinergic synapses.


Key words: Glycine receptors • Kinetics • Patch clamp




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