The role of the nAChR subunits ?5, ?2, and ?4 on synaptic transmission in the mouse superior cervical ganglion.

ABSTRACT: Our previous immunoprecipitation analysis of nicotinic acetylcholine receptors (nAChRs) in the mouse superior cervical ganglion (SCG) revealed that approximately 55%, 24%, and 21% of receptors are comprised of ?3?4, ?3?4?5, and ?3?4?2 subunits, respectively. Moreover, mice lacking ?4 subunits do not express ?5-containing receptors but still express a small number of ?3?2 receptors. Here, we investigated how synaptic transmission is affected in the SCG of ?5?4-KO and ?5?2-KO mice. Using an ex vivo SCG preparation, we stimulated the preganglionic cervical sympathetic trunk and measured compound action potentials (CAPs) in the postganglionic internal carotid nerve. We found that CAP amplitude was unaffected in ?5?4-KO and ?5?2-KO ganglia, whereas the stimulation threshold for eliciting CAPs was significantly higher in ?5?4-KO ganglia. Moreover, intracellular recordings in SCG neurons revealed no difference in EPSP amplitude. We also found that the ganglionic blocking agent hexamethonium was the most potent in ?5?4-KO ganglia (IC50 : 22.1 ?mol/L), followed by ?5?2-KO (IC50 : 126.7 ?mol/L) and WT ganglia (IC50 : 389.2 ?mol/L). Based on these data, we estimated an IC50 of 568.6 ?mol/L for a receptor population consisting solely of ?3?4?5 receptors; and we estimated that ?3?4?5 receptors comprise 72% of nAChRs expressed in the mouse SCG. Similarly, by measuring the effects of hexamethonium on ACh-induced currents in cultured SCG neurons, we found that ?3?4?5 receptors comprise 63% of nAChRs. Thus, in contrast to our results obtained using immunoprecipitation, these data indicate that the majority of receptors at the cell surface of SCG neurons consist of ?3?4?5.

SUBMITTER: Simeone X 

PROVIDER: S-EPMC6424856 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature