The role of sodium influx mediated by nicotinic receptors as an initial event in trans-synaptic induction of tyrosine hydroxylase in adrenergic neurons

1.Isolated superior cervical ganglia of the rat were incubated for 2–30 min (37°C) in Krebs' solution or tissue culture medium (BGJb) containing ²²Na and then washed for 30 min in ice-cold ²²Na-free Krebs' solution (to clear the extracellular space). The radioactivity remaining in the ganglia was taken as a measure of ²²Na influx into the intracellular compartment of the ganglion.2.Addition of cholinomimetics (100 µM nicotine or 100 µM carbachol) to the incubation medium led to an increase in ²²Na influx. This increase reached maximal values after 10 min of incubation; it was more pronounced after incubation in Krebs' solution than in BGJb medium.3.While chlorisondamine (3 µM) or dopamine (100 µM) greatly reduced the carbachol-induced ²²Na influx, tetrodotoxin (2 µM) did not have any effect.4.In ganglia obtained from animals treated with 6-hydroxydopamine in the early postnatal phase (resulting in an extensive destruction of peripheral sympathetic neurons) neither carbachol (100 µM) nor nicotine (100 µM) produced an increase in ²²Na influx demonstrating that the intraneuronal compartment is responsible for this enhanced influx.5.The effects of dopamine, chlorisondamine and tetrodotoxin on the carbachol-induced ²²Na uptake into superior cervical ganglia are similar to their effects on carbachol-mediated induction of tyrosine hydroxylase in superior cervical ganglia kept in tissue culture (Thoenen and Otten 1977b). It is concluded that the induction of tyrosine hydroxylase via nicotinic receptors is closely linked to the enhanced sodium influx into the adrenergic neurons mediated by the same receptors.