ACETYLCHOLINE POTENTIATES ACETYLCHOLINE-INDUCED INCREASES IN K+ CURRENT IN CAT ATRIAL MYOCYTES

A nystatin-perforated patch whole cell recording method was used to study the effects of acetylcholine (ACh) on ACh-induced K+ currents in atrial myocytes isolated from cat hearts. The general protocol involved an initial 4-min exposure to ACh (ACh(1)), followed by a 4-min washout in ACh-free Tyrode solution and then a second 4-min ACh exposure (ACh2). Voltage ramps (40 mV/s) between -130 and +30 mV were used to assess changes in total membrane conductance. ACh2 (10 mu M) induced an increase in K+ conductance that was significantly larger than that induced by ACh(1) (10 mu M) at voltages both negative and positive to the reversal potential. The potentiated current induced by ACh2 reversed at about -80 mV and inwardly rectified at voltages positive to the reversal potential. External Ba2+ (5 mM) or tetraethylammonium (10 mM) abolished all ACh(2)-induced increases in membrane conductance. The sensitivity to K+ channel blockers, reversal potential, and the rectifying properties indicate that the current potentiated by ACh(2) is a K+ current. Atropine (1 mu M) blocked all effects of ACh on K+ currents. Potentiation of K+ current by ACh(2) required 1) ACh(1) concentrations greater than or equal to 1 mu M, 2) ACh(1) duration greater than or equal to 2 min, and 3) recovery interval greater than or equal to 2 min. We conclude that an initial exposure to ACh potentiates subsequent ACh-induced increases in K+ current. ACh-induced potentiation depends on the concentration and duration of the initial ACh exposure and the recovery interval between consecutive ACh exposures. Depending on prevailing conditions, an initial exposure to ACh can cause either desensitization and/or potentiation of subsequent ACh-induced increases in K+ conductance.