Nicotinic Cholinergic Receptors in the Rat Cerebellum: Multiple Heteromeric Subtypes

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Abstract
Nicotinic receptors (nAChRs) in the cerebellum have been implicated in the pathology of autism spectrum disorders (Lee et al., 2002; Martin-Ruiz et al., 2004). The subtypes of nAChRs in the cerebellum are not known in any detail, except that, in addition to the homomeric α7 subtype, there appears to be one or more heteromeric subtypes consisting of combinations of α and β subunits. To begin to better understand the potential roles of these heteromeric nAChRs in cerebellar circuitry and their potential as targets for nicotinic drugs, we investigated their subunit composition. Using subunit-selective antibodies in sequential immunoprecipitation assays, we detected six structurally distinct heteromeric nAChR populations in the rat cerebellum. Among these were several subtypes that have not been encountered previously, including α3α4β2 and α3α4β4 nAChRs. This diversity suggests that nAChRs play multiple roles in cerebellar physiology.