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Publication : The role of the nAChR subunits α5, β2, and β4 on synaptic transmission in the mouse superior cervical ganglion.

First Author  Simeone X Year  2019
Journal  Physiol Rep Volume  7
Issue  6 Pages  e14023
PubMed ID  30891952 Mgi Jnum  J:290743
Mgi Id  MGI:6442601 Doi  10.14814/phy2.14023
Citation  Simeone X, et al. (2019) The role of the nAChR subunits alpha5, beta2, and beta4 on synaptic transmission in the mouse superior cervical ganglion. Physiol Rep 7(6):e14023
abstractText  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 alpha3beta4, alpha3beta4alpha5, and alpha3beta4beta2 subunits, respectively. Moreover, mice lacking beta4 subunits do not express alpha5-containing receptors but still express a small number of alpha3beta2 receptors. Here, we investigated how synaptic transmission is affected in the SCG of alpha5beta4-KO and alpha5beta2-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 alpha5beta4-KO and alpha5beta2-KO ganglia, whereas the stimulation threshold for eliciting CAPs was significantly higher in alpha5beta4-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 alpha5beta4-KO ganglia (IC50 : 22.1 mumol/L), followed by alpha5beta2-KO (IC50 : 126.7 mumol/L) and WT ganglia (IC50 : 389.2 mumol/L). Based on these data, we estimated an IC50 of 568.6 mumol/L for a receptor population consisting solely of alpha3beta4alpha5 receptors; and we estimated that alpha3beta4alpha5 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 alpha3beta4alpha5 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 alpha3beta4alpha5.
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