Subunit composition and kinetics of the Renshaw cell heteromeric nicotinic receptors

In Renshaw cells (RCs) of newborn mice, activation of motoneurons elicits a four-component synaptic current (EPSC) mediated by two glutamate receptors and two nicotinic receptors (nAChRs). We have analyzed the nicotinic component of the EPSC which is blocked by dihydro-beta-erythroidine (DH beta E) with the dual objective of identifying the nAChR subunits involved and of understanding the kinetics of the response. The sensitivity to DH beta E of the peak of the EPSC was differentially affected by genetic deletion of three specific nAChR subunits: alpha 2, beta 2 in and beta 4. The comparison of these effects with published findings on recombinant receptors suggests that, in WT mice, two heteromeric assemblies, alpha 4 beta 2 and alpha 2 beta 4, coexist in variable proportions in a given RC. Some results seem to require, however, the involvement of an additional subunit. The effects of DH beta E on the decay of the EPSCs were compared in WT mice and in PRiMA(-/-) mice, in which the decay is prolonged by the absence of central acetylcholinesterase. In PRiMA(-/-) mice DH beta E shortened the decay of the EPSC. In WT mice it did not alter the decay but reduced the amplitude of both components of the EPSC. The results can be interpreted by assuming that the nAChRs exist in two stoichiometries, subsynaptic "low sensitivity" nAChRs and extrasynaptic "high sensitivity" nAChRs activated by spillover. (C) 2013 Elsevier Inc. All rights reserved.