| First Author | Lamotte d'Incamps B | Year | 2018 |
| Journal | J Neurosci | Volume | 38 |
| Issue | 21 | Pages | 4943-4956 |
| PubMed ID | 29724797 | Mgi Jnum | J:262235 |
| Mgi Id | MGI:6159209 | Doi | 10.1523/JNEUROSCI.0070-18.2018 |
| Citation | Lamotte d'Incamps B, et al. (2018) Stoichiometry of the Heteromeric Nicotinic Receptors of the Renshaw Cell. J Neurosci 38(21):4943-4956 |
| abstractText | Neuronal nicotinic acetylcholine receptors (nAChRs) are pentamers built from a variety of subunits. Some are homomeric assemblies of alpha subunits, others heteromeric assemblies of alpha and beta subunits which can adopt two stoichiometries (2alpha:3beta or 3alpha:2beta). There is evidence for the presence of heteromeric nAChRs with the two stoichiometries in the CNS, but it has not yet been possible to identify them at a given synapse. The 2alpha:3beta receptors are highly sensitive to agonists, whereas the 3alpha:2beta stoichiometric variants, initially described as low sensitivity receptors, are indeed activated by low and high concentrations of ACh. We have taken advantage of the discovery that two compounds (NS9283 and Zn) potentiate selectively the 3alpha:2beta nAChRs to establish (in mice of either sex) the presence of these variants at the motoneuron-Renshaw cell (MN-RC) synapse. NS9283 prolonged the decay of the two-component EPSC mediated by heteromeric nAChRs. NS9283 and Zn also prolonged spontaneous EPSCs involving heteromeric nAChRs, and one could rule out prolongations resulting from AChE inhibition by NS9283. These results establish the presence of 3alpha:2beta nAChRs at the MN-RC synapse. At the functional level, we had previously explained the duality of the EPSC by assuming that high ACh concentrations in the synaptic cleft account for the fast component and that spillover of ACh accounts for the slow component. The dual ACh sensitivity of 3alpha:2beta nAChRs now allows to attribute to these receptors both components of the EPSC.SIGNIFICANCE STATEMENT Heteromeric nicotinic receptors assemble alpha and beta subunits in pentameric structures, which can adopt two stoichiometries: 3alpha:2beta or 2alpha:3beta. Both stoichiometric variants are present in the CNS, but they have never been located and characterized functionally at the level of an identified synapse. Our data indicate that 3alpha:2beta receptors are present at the spinal cord synapses between motoneurons and Renshaw cells, where their dual mode of activation (by high concentrations of ACh for synaptic receptors, by low concentrations of ACh for extrasynaptic receptors) likely accounts for the biphasic character of the synaptic current. More generally, 3alpha:2beta nicotinic receptors appear unique by their capacity to operate both in the cleft of classical synapses and at extrasynaptic locations. |
