Allosteric potentiation of glycine receptor chloride currents by glutamate英文文献.pdfVIP

a r t I C l e S Allosteric potentiation of glycine receptor chloride currents by glutamate Jun Liu1,3, Dong Chuan Wu1–3 Yu Tian Wang1,2 Neuronal excitability in the CNS is primarily controlled by a balance between synaptic excitation and inhibition. In the brainstem and spinal cord, synaptic excitation and inhibition are mediated by the excitatory transmitter glutamate acting on ionotropic glutamate receptor–gated cationic channels and the inhibitory transmitter glycine acting on glycine receptor (GlyR)-gated chloride channels. We found that glutamate and its analog ligands potentiated GlyR-mediated currents in both cultured spinal . neurons and spinal cord slices of rats. This potentiation was not dependent on activation of any known glutamate receptor and d e v manifested as an increase in single-channel open probability. Moreover, this glutamate potentiation was seen in HEK293 cells r e that transiently expressed GlyRs. Our data strongly suggest that glutamate allosterically potentiates GlyR-gated chloride channels, s e thereby blurring the traditional distinction between excitatory and inhibitory transmitters. Such a rapid homeostatic regulatory r s mechanism may be important for tuning functional balance between synaptic excitation and inhibition in the CNS. t h g i r l Neuronal excitability is fundamental to neuronal function and is (10 μM). The synaptic events can be characterized into two major l A primarily controlled by a fine balance between synaptic excitation populations on the basis of their kinetics: a fast population, which . and inhibition. In the mammalian CNS, synaptic excitation is chiefly had a mean 10–90% rising time of 0.77 ms ± 0.06 and a decay time c n I