Interaction between nerve-related acetylcholine and bath applied agonists at the frog end-plate.

1. The interaction between acetylcholine (ACh) and carbachol (CCh) has been studied at the frog end-plate. The conditioning agonist, CCh, can cause desensitization (reduction of the ACh test response) and potentiation (increase of the test response). 2. Nerve-evoked end-plate currents (e.p.c.s), minature e.p.c.s and "slow" responses to ACh ionophoresis can all be potentiated by bath or ionophoretically applied CCh. 3. Since potentiation was found to be particularly visible at low temperatures, most experiments were performed at 5-8 degrees C. Potentiation results in an increase of both e.p.c. amplitude and e.p.c. decay time. Potentiated e.p.c.s teminate with a slow tail, the amplitude of which shows a high voltage sensitivity. Potentiation increases with CCh concentration (range studied 0-100 microM). It appears to persist throughout the application of CCh, even when desensitization is apparently the dominant phenomenon. 4. It is suggested that cross-potentiation of ACh by CCh results from the formation of intermediate non-conducting CCh-receptor complexes which have a high probability of being subsequently activated by ACh, yielding a conducting ACh-CCh-receptor complex. 5. Desensitization induced by fast bath application of CCh (or ACh) develops in two phases and can be fitted by the sum of two exponentials. Their time constants are in the second and the minute range, respectively. 6. The possibility that the slow phase is linked to the presence of agonist inside the cell is rejected.