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1. The surface chemosensitivity to iontophoretically applied acetylcholine (ACh) of single nerve cells in the cardiac ganglion of the mudpuppy was examined. 2. Some synapses on the neurones can be recognized in the living preparation with differential interference contrast optics. Identified synaptic regions of the ganglion cells were more sensitive to ACh than were other areas. The mean sensitivity of synaptic areas was 509 mV/nC, but that of random spots on the cell surface (which were mainly non-synaptic) was only 190 mV/nC. The mean rise time of ACh responses at synapses was 23 msec and at random spots was 36 msec. These data suggest that the density of ACh receptors is highest under the synapses on the post-synaptic membrane. 3. When some, but not all, of the presynaptic terminals on the ganglion cells are destroyed by cutting the vagus nerve, the sensitivity of the entire surface membrane to applied ACh increases. This increase in sensitivity reaches a maximum about 4-6 weeks after the operation. 4. Synaptic transmission at excitatory collateral synapses which remain after vagal degeneration is not altered by this hypersensitivity. 5. Neurones from ganglia which have been isolated and maintained in organ culture also become hypersensitive to applied ACh. this heightened chemosensitivity deveoops much faster in vitro; hypersensitivity in cultured ganglia becomes manifest within 4-5 days, in contrast with 4-6 weeks after vagus degeneration in vivo.

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