LACK OF NICOTINIC SUPERSENSITIVITY IN FROG SYMPATHETIC NEURONS FOLLOWING DENERVATION

The sensitivity of bull-frog sympathetic neurons to nicotinic, cholinergic agonists was studied in both normal (control) and surgically denervated ganglia. Using gross extracellular recording, the sensitivity to acetylcholine (ACh) increased 18-fold following denervation, while that to carbachol (CCh) was unchanged. Normal ganglia showed a similar sensitivity increase after inhibition of cholinesterase. This suggests that the rise in ACh sensitivity is due to reduced cholinesterase activity, not to true supersensitivity. There was no significant difference in resting membrane potential or input resistance between normal and denervated neurons. Neurons denervated for 7-50 days showed no significant change in sensitivity to ACh or CCh applied iontophoretically at a distance of 10 .mu.m from the cell surface. In control ganglia, localized iontophoretic application of ACh or CCh applied iontophoretically at a distance of 10 .mu.M from the cell surface. In control ganglia, localized iontophoretic application of ACh revealed an uneven distribution of sensitivity which is attributed to the localization of receptors to synaptic areas. Days (14) after denervation, the geometric mean sensitivity to focally applied ACh was not significantly different from that found in conttrol ganglia. The variation in sensitivity to focally applied ACh at randomly chosen sites on denervated neurons was as great as that found in control ganglia. Denervation does not cause frog sympathetic neurons to become supersensitive to ACh. The apparent increase in nicotinic ACh sensitivity observed using extracellular recording from whole ganglia is due not to a change in the number or distribution of ACh receptors, but to a decrease in cholinesterase activity.