The kinetics of desensitization of
acetylcholine-evoked Cl conductance increased response of Aplysia RC neurons of the abdominal
ganglion were studied under voltage-clamp conditions for comparison with results of similar studies on
acetylcholine Na and K responses. The response evoked by
acetylcholine on RC neurons was an outward current at resting potential (about -45 mV) that reversed at about -65 mV and was blocked by
D-tubocurarine and
strychnine but not
hexamethonium and was not activated by
arecoline. From the current-voltage relation this response can be ascribed to a pure conductance increase to Cl. The apparent KD was 40.6 microM. Upon prolonged exposure to
acetylcholine the response peaked within 200-400 ms, and then decayed to a plateau current in the continued presence of the agonist. The peak and plateau currents reversed at the same potential, indicating that there had not been significant redistribution of Cl. The current decay in every cell was best fit by a double exponential function plus a constant, and the average time constants were tau fast = 1.8 +/- 0.2 s and tau slow = 16.2 +/- 1.0 s. Both components were slowed by cooling. While tau fast did not change with dose, tau slow increased with dose. Both components accelerated with hyperpolarization and upon application of
trifluoperazine (2 microM). These results are consistent with the interpretation that desensitization of the
acetylcholine Cl response is composed of two independent processes. This conclusion is the same as that derived from studies of the
acetylcholine Na and K responses, and is in general consistent with desensitization being a property of a common
acetylcholine receptor, and independent of the ionic selectivity of the associated channel. There are, however, significant differences in voltage, temperature and
trifluoperazine dependence of the two components of the three ionic responses which may reflect influence of the different
ion channels and/or transduction mechanisms.