Functional involvement of sulphonylurea receptor (SUR) type 1 and 2B in the activity of pig urethral ATP‐sensitive K + channels

We have investigated the possible roles of sulphonylurea receptor (SUR) type 1 and 2B in the activity of pig urethral ATP‐sensitive K + channels (K ATP channels) by use of patch‐clamp and reverse transcriptase–polymerase chain reaction (RT–PCR) techniques. In voltage‐clamp experiments, not only diazoxide, a SUR1 and weak SUR2B activator, but also pinacidil, a selective SUR2 activator, caused an inward current at a holding potential of −50 mV in symmetrical 140 m M K + conditions. Gliclazide (1 μ M ), a selective SUR1 blocker, inhibited the 10 μ M pinacidil‐induced currents ( K i =177 μ M ) and the 500 μ M diazoxide‐induced currents (high‐affinity site, K i1 =5 n M ; low‐affinity site, K i2 =108 μ M ) at −50 mV. Application of tolbutamide (100 μ M ) reversibly caused an inhibition of the 500 μ M diazoxide‐induced current at –50 mV. MCC‐134, a SUR type‐specific K ATP channel regulator (1–100 μ M ), produced a concentration‐dependent inward K + current, which was suppressed by the application of glibenclamide at −50 mV. The amplitude of the MCC‐134 (100 μ M )‐induced current was approximately 50% of that of the 100 μ M pinacidil‐induced currents. Using cell‐attached configuration, MCC‐134 activated a glibenclamide‐sensitive K ATP channel which was also activated by pinacidil. RT–PCR analysis demonstrated the presence of SUR1 and SUR2B transcripts in pig urethra. These results indicate that both SUR1 and SUR2B subunits play a functional role in regulating the activity of pig urethral K ATP channels and that SUR1 contributes less than 25% to total K ATP currents.British Journal of Pharmacology (2003) 139 , 652–660. doi: 10.1038/sj.bjp.0705268