Loss of extrasynaptic acetylcholine sensitivity upon reinnervation of parasympathetic ganglion cells.

1. The extrasynaptic acetylcholine sensitivity of frog cardiac ganglion cells was measured both after denervation and during the early stages of reinnervation by preganglionic axons. Sensitivity was measured by ionophoretic application of acetylcholine (ACh) to randomly chosen sites on ganglion cell bodies. 2. Extrasynaptic sensitivity rose gradually following denervation and after 3 weeks reached a mean value of approximately 1000 mV/nC. 3. Reinnervation of the cardiac ganglion began about 3 weeks after nerve crush. The ACh sensitivity of ganglion cells fell markedly during the 23--31 day period, to a mean of 184 mV/nC. None of forty-three neurones studied during that period received synaptic inputs sufficient to generate action potentials. 4. Twenty-nine of the forty-three neurones examined 23--31 days after nerve crush had not yet received detectable synaptic inputs, yet even these cells had markedly reduced ACh sensitivity. 5. When reinnervation of cardiac ganglia was delayed by resecting the preganglionic nerves, ACh sensitivity was reduced slightly (43%) between 14--21 and 23--31 days after surgery. Thus, most of the sixfold reduction in sensitivity that occurs during this time after nerve crush is a specific effect of reinnervation. 6. We conclude that loss of extrasynaptic receptors coincides with, or may even precede, the earliest physiological signs of synapse formation. Restoration of action potential activity in the ganglion cells is not essential to initiate this loss.