Stoichiometry of the Heteromeric Nicotinic Receptors of the Renshaw Cell.

d'Incamps, Boris Lamotte; Zorbaz, Tamara; Dingova, Dominika; Krejci, Eric; Ascher, Philippe

Neuronal nicotinic acetylcholine receptors (nAChRs) are pentamers built from a variety of subunits. Some are homomeric assemblies of "subunits, others heteromeric assemblies of α and β subunits which can adopt two stoichiometries (2α:3β or 3α:2β). 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 2α3β receptors are highly sensitive to agonists, whereas the 3α:2β 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 3α:2β 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 3α:2β 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 3α:2β nAChRs now allows to attribute to these receptors both components of the EPSC.

NICOTINIC acetylcholine receptors; STOICHIOMETRY; RENSHAW cells; MOTOR neurons; ZINC

Journal of Neuroscience, 2018, Vol 38, Issue 21, p4943

0270-6474

Academic Journal

10.1523/JNEUROSCI.0070-18.2018