Abstract
We investigated the functional expression of nicotinic acetylcholine receptors (nAChRs) in heterogeneous populations of dissociated rat and mouse lumbar dorsal root ganglion (DRG) neurons by calcium imaging. By this experimental approach, it is possible to investigate the functional expression of multiple receptor and ion-channel subtypes across more than 100 neuronal and glial cells simultaneously. Based on nAChR expression, DRG neurons could be divided into four subclasses: (1) neurons that express predominantly α3β4 and α6β4 nAChRs; (2) neurons that express predominantly α7 nAChRs; (3) neurons that express a combination of α3β4/α6β4 and α7 nAChRs; and (4) neurons that do not express nAChRs. In this comparative study, the same four neuronal subclasses were observed in mouse and rat DRG. However, the expression frequency differed between species: substantially more rat DRG neurons were in the first three subclasses than mouse DRG neurons, at all developmental time points tested in our study. Approximately 70–80% of rat DRG neurons expressed functional nAChRs, in contrast to only ~15–30% of mouse DRG neurons. Our study also demonstrated functional coupling between nAChRs, voltage-gated calcium channels, and mitochondrial Ca2+ transport in discrete subsets of DRG neurons. In contrast to the expression of nAChRs in DRG neurons, we demonstrated that a subset of non-neuronal DRG cells expressed muscarinic acetylcholine receptors and not nAChRs. The general approach to comparative cellular neurobiology outlined in this paper has the potential to better integrate molecular and systems neuroscience by uncovering the spectrum of neuronal subclasses present in a given cell population and the functionally integrated signaling components expressed in each subclass.
Highlights
Progress in investigating the mammalian nervous system has largely been achieved by molecular and systems neuroscientists at two very disparate levels
Several related experimental protocols were used to assess the functional expression of particular nicotinic acetylcholine receptors (nAChRs) subtypes, as illustrated in the figures and as described in Materials and Methods
In this study, we characterized the spectrum of rat and mouse dorsal root ganglion (DRG) neurons with regard to their nAChR-expression profiles, using a cellular neuropharmacological platform that we established previously (Teichert et al, 2012a,b)
Summary
Progress in investigating the mammalian nervous system has largely been achieved by molecular and systems neuroscientists at two very disparate levels. Functional complexity is created because individual gene products can combine to form various heteromeric receptor- and ion-channel subtypes in different neuronal subclasses. These factors create the functionally divergent neurons with distinct physiological roles found at any anatomical locus of the nervous system. The basic strategy is to monitor functional activity of specific receptor- and ion-channel subtypes in more than 100 individual cells simultaneously from a heterogeneous cell population, as we described previously (Teichert et al, 2012a,b) Using this experimental approach, we characterized dissociated rat and mouse lumbar dorsal-root ganglion (DRG) neurons that express functional nAChRs, and identified the particular nAChR subtypes expressed in different neuronal subclasses. This work represents a critical first step toward that goal
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