D-myo-inositol 1,4,5-trisphosphate (IP(3)) plays an important role in signal transduction. It releases Ca(2+) from intracellular sites, which activates the Ca(2+)-dependent channels such as large-conductance Ca(2+)-activated potassium channels (BK channels). The present study was therefore designed to determine if the activity of BK channels in porcine coronary artery smooth muscle cells was increased by IP(3). Using the inside-out patch-clamp technique, the activity of single BK channels was recorded in porcine coronary artery smooth muscle cells. In excised inside-out membrane patches, IP(3) (10-50 micromol/L) enhanced the open probability (Po) of BK channels in a dose-dependent manner in the intracellular side of inside-out patches and its effect was almost completely abolished by washout. The open-state probability of the BK channels increased from a control level of 0.0402+/-0.0152 to 0.1365+/-0.0212 (20 micromol/L IP(3)) and 0.1865+/-0.0175 (30 micromol/L IP(3)). IP(3) decreased the mean close time markedly, but had no effect on the amplitude of BK channels. The activation of IP(3) on BK channels did not decline. The metabolite of IP(3) had no obvious effect on BK channels. This study provides evidence that IP(3) activates BK channels in porcine coronary artery smooth muscle cells in a dose-dependence manner.