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First published online on April 17, 2008.
Copyright © 2008 by The Physiological Society
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jphysiol.2008.151050v1
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Received January 11, 2008
Revised February 14, 2008
Accepted after revision April 15, 2008

How do tonic glutamatergic synapses evade receptor desensitization?

Ji-Jie Pang1, Fan Gao1, Andrew Barrow1, Roy A. Jacoby1, and Samuel M Wu1*

1 Baylor College of Medicine

* To whom correspondence should be addressed. E-mail: swu{at}bcm.tmc.edu.

Photoreceptor output synapses are the best known tonic chemical synapses in the nervous system, in which glutamate is continuously released in darkness, activating AMPA/kainate receptors in postsynaptic neurons. It has been shown that glutamate receptors in certain types of second-order retinal cells are largely desensitized in darkness, leading to small postsynaptic currents and reduced response dynamic ranges. Here we show that the tonic glutamatergic synapses between photoreceptors and rod-dominated hyperpolarizing bipolar cells (HBCRs) in the salamander retina evade postsynaptic receptor desensitization by using (1) multiple invaginating ribbon junctions as releasing sites for low frequency, synchronized multiquantal release at each site; and (2) the GluR-4 AMPA receptors as the postsynaptic receptors. The multiquantal events exhibit faster decay time than the GluR-4 receptor desensitization time constant and therefore self-desensitization is minimized, and the average inter-event duration in darkness is much longer than the GluR-4 desensitization recovery time and thus mutual desensitization is avoided. Consequently, the HBCRs are not desensitized in darkness, allowing light signals to be encoded by the full operating range of the glutamate-gated postsynaptic currents. Our study illustrates for the first time how a tonic glutamatergic synapse avoids postsynaptic receptor desensitization, a strategy that may be shared by many other synapses in the nervous system that need extended operation capacity.


Key words: Amino acid transmitters • Bipolar cell • Desensitization







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