Tischkau_2014_Neurosci.Lett_563_107

Hypothalamic histaminergic tuberomammillary (TM) neurons in rats express high densities of nicotinic acetylcholine receptors (nAChRs) whose Ca(2+) permeability, kinetic and pharmacological properties are similar to those of heterologous homomeric alpha7 nAChRs. However, native alpha7 nAChR subunits can co-assemble with beta or alpha5 nAChR subunits to form functional heteromeric alpha7-containing alpha7beta or alpha7alpha5 nAChRs with kinetics and pharmacology similar to those of alpha7 homomers. Therefore, although TM nAChRs have been used as an ex vivo model of functional alpha7 homomers, the molecular makeup of TM nAChRs has not been determined and the expression of functional alpha7-containing heteromers in TM neurons has not been excluded. To determine the profile of TM nAChR subunit transcripts, we have conducted single-cell qRT-PCR experiments using acutely dissociated TM neurons in rats. TM neurons were found to express transcripts of only principal alpha3, alpha6 and alpha7 nAChR subunits. Transcripts of other known mammalian neuronal subunits (alpha2, alpha4-5, alpha9-10, beta2-4) were not detected. In the absence of beta and alpha5 subunits, the expression of functional alpha7-containing heteromers in TM neurons is highly unlikely because principal alpha3, alpha6 and alpha7 nAChR subunits alone are not known to form functional heteromeric nAChRs. These results support the exclusive expression of native functional alpha7 homomers in rat TM neurons and introduce these neurons as a unique reliable source of native functional homomeric alpha7 nAChRs suitable for ex vivo and in vitro pharmacological assays in developing selective alpha7 nAChR agents.