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

Our previous immunoprecipitation analysis of nicotinic acetylcholine receptors ( nAChR s) in the mouse superior cervical ganglion ( SCG ) revealed that approximately 55%, 24%, and 21% of receptors are comprised of α 3 β 4, α 3 β 4 α 5, and α 3 β 4 β 2 subunits, respectively. Moreover, mice lacking β 4 subunits do not express α 5‐containing receptors but still express a small number of α 3 β 2 receptors. Here, we investigated how synaptic transmission is affected in the SCG of α 5 β 4‐ KO and α 5 β 2‐ KO mice. Using an ex vivo SCG preparation, we stimulated the preganglionic cervical sympathetic trunk and measured compound action potentials ( CAP s) in the postganglionic internal carotid nerve. We found that CAP amplitude was unaffected in α 5 β 4‐ KO and α 5 β 2‐ KO ganglia, whereas the stimulation threshold for eliciting CAP s was significantly higher in α 5 β 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 α 5 β 4‐ KO ganglia ( IC 50 : 22.1  μ mol/L), followed by α 5 β 2‐ KO ( IC 50 : 126.7  μ mol/L) and WT ganglia ( IC 50 : 389.2  μ mol/L). Based on these data, we estimated an IC 50 of 568.6  μ mol/L for a receptor population consisting solely of α 3 β 4 α 5 receptors; and we estimated that α 3 β 4 α 5 receptors comprise 72% of nAChR s expressed in the mouse SCG . Similarly, by measuring the effects of hexamethonium on AC h‐induced currents in cultured SCG neurons, we found that α 3 β 4 α 5 receptors comprise 63% of nAChR s. 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 α 3 β 4 α 5.