Processes involved in activation of the acetylcholine (ACh) receptor-operated K+ current (IK) were examined in atrial cells isolated from guinea pig using a "concentration-clamp" technique. This approach allows for the intracellular perfusion and the rapid change of external solution (time constant 4 ms) with cell-attached condition under a single-electrode voltage-clamp condition. The ACh-induced IK increased in a sigmoidal fashion with increasing concentrations of ACh. The Ka value estimated from the concentration-response curve was 3 X 10(-7) M, and the Hill coefficient was 1.0. The activation phase was accelerated not only by increasing the concentration of ACh but also by elevating the temperature. Before activation of the current, there was a brief latent period after the application of ACh. The latent period was shortened considerably with the increase in ACh concentration and in temperature, i.e., 267 +/- 20 ms at 18 degrees C, 98 +/- 11 ms at 26 degrees C, and 44 +/- 6 ms at 37 degrees C for 10(-6) M ACh. These results suggest that the latent period of ACh response seems to be the time lag needed for the activation of K+ channels using remote sensor.