In smooth muscle cells isolated from cerebral blood vessels, histamine activates Cl- channels through an elevation of intracellular Ca2+. We investigated whether Cl- currents were also evoked by adenosine triphosphate (ATP) or caffeine in isolated smooth muscle cells from the rabbit basilar artery using the perforated patch-clamp technique. Bath application of 10 microM ATP or 1 mM caffeine (holding potential -60 mV) activated transient inward currents. With prolonged bath application of 10 microM ATP or 1 mM caffeine, oscillatory inward current were sporadically generated. At a holding potential of -40 mV, transient Cl- currents were induced by 10 microM histamine, 10 microM ATP, and 1 mM caffeine, following activation of a K+ current. At -10 or -20 mV, histamine predominantly activated the K+ current. A repetitively activated outward current was induced by membrane depolarization. These results suggest that oscillations in intracellular Ca2+ induced by histamine, ATP, and caffeine caused Cl(-)-current activation at the resting membrane potential. This Cl- current may depolarize the membrane and, thus activate voltage-dependent currents, including a Ca(2+)-dependent K+ current. Both the Ca(2+)-dependent K+ and Cl- currents induced by various stimuli may contribute to the modulation of Ca2+ influx by reinforcing membrane depolarization.