Effects of U-37883A on intracellular Ca ²⁺-activated large-conductance K ⁺ channels in pig proximal urethral myocytes

Kinetic studies of U-37883A (4-morpholinecarboximidine-N-1-adamantyl- N′-cyclohexyl-hydrochloride), a vascular ATP-sensitive K ⁺ channel (K _ATP channel) blocker, were performed on pig urethral myocytes to investigate inhibitory effects on large-conductance intracellular Ca ²⁺-sensitive K ⁺ channels (i.e., BK _Ca channels; 225 pS K ⁺ channels) by use of single-channel recordings (outside-out and inside-out configuration). BK _Ca channels in pig urethral smooth muscles showed extracellular iberiotoxin (300 nM) sensitivity and voltage dependency. The α subunit of BK _Ca channel proteins was detected in the membrane fraction by use of Western blot technique. Application of U-37883A (≥10 μM) reduced the activity of BK _Ca channels in a concentration-dependent manner, not only by decreasing mean openlife time but also by prolonging the mean closed time. These results shows that U-37883A affects channels other than the vascular K _ATP channel, and demonstrates how it inhibits the activities of BK _Ca channels in urethral smooth muscles.