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This Article Full Text Full Text (PDF) All Versions of this Article: 553/2/369    most recent jphysiol.2003.052142v2 jphysiol.2003.052142v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mangin, J. M. Articles by Legendre, P. Search for Related Content PubMed PubMed Citation Articles by Mangin, J. M. Articles by Legendre, P.

Kinetic properties of the ₂ homo-oligomeric glycine receptor impairs a proper synaptic functioning

J. M. Mangin, M. Baloul, L. Prado de Carvalho, B. Rogister*, J. M. Rigo* and P. Legendre

Ionotropic glycine receptors (GlyRs) are present in the central nervous system well before the establishment of synaptic contacts. Immature nerve cells are known, at least in the spinal cord, to express ₂ homomeric GlyRs, the properties of which are relatively unknown compared to those of the adult synaptic form of the GlyR (mainly ₁/ heteromeres). Here, the kinetics properties of GlyRs at the single-channel level have been recorded in real-time by means of the patch-clamp technique in the outside-out configuration coupled with an ultra-fast flow application system (< 100 µs). Recordings were performed on chinese hamster ovary (CHO) cells stably transfected with the ₂ GlyR subunit. We show that the onset, the relaxation and the desensitisation of ₂ homomeric GlyR-mediated currents are slower by one or two orders of magnitude compared to synaptic mature GlyRs and to other ligand-gated ionotropic channels involved in fast synaptic transmission. First latency analysis performed on single GlyR channels revealed that their slow activation time course was due to delayed openings. When synaptic release of glycine was mimicked (1 mM glycine; 1 ms pulse duration), the opening probability of ₂ homomeric GlyRs was low (P_o 0.1) when compared to mature synaptic GlyRs (P_o = 0.9). This low P_o is likely to be a direct consequence of the relatively slow activation kinetics of ₂ homomeric GlyRs when compared to the activation kinetics of mature ₁/ GlyRs. Such slow kinetics suggest that embryonic ₂ homomeric GlyRs cannot be activated by fast neurotransmitter release at mature synapses but rather could be suited for a non-synaptic paracrine-like release of agonist, which is known to occur in the embryo.

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