The effect of adenosine on Ca(2+)-dependent K(+) currents was studied in freshly isolated smooth muscle cells from rat mesenteric artery. Perforated-patch recordings showed that adenosine induced transient outward currents and an overall increase in the averaged currents at higher depolarizing potentials. The changes in current activity induced by adenosine could be blocked by iberiotoxin. The transient outward currents were not dependent directly on external Ca(2+) and could be induced after brief exposure to Ca(2+)-free solutions. In conventional whole-cell recordings, transient outward currents were also induced by adenosine when a low EGTA concentration of 0.1 mM was included in the pipette solution. Adenosine was not effective in inducing increases in outward currents when a higher concentration of 5.0 mM EGTA was used. Ryanodine and thapsigargin were also effective in blocking the effect of adenosine. These observations suggest that adenosine may activate Ca(2+)-dependent K(+) currents by inducing Ca(2+) release from ryanodine-sensitive channels in the sarcoplasmic reticulum of rat mesenteric arterial cells.