Submitted on January 2, 2008
Revised on August 18, 2008
Accepted on September 4, 2008
Stimulation of 
3-adrenoceptors relaxes rat urinary bladder smooth muscle via activation of the large conductance Ca2+-activated K+ (BK) channels
Kiril L. Hristov1, Xiangli Cui1, Sean M Brown1, Lei Liu1, Whitney F. Kellett1, and Georgi V. Petkov1*
1 University of South Carolina
* To whom correspondence should be addressed. E-mail: petkov{at}cop.sc.edu.
We investigated the role of large conductance Ca2+-activated K+ (BK) channels in 
3-adrenoceptor (3-AR)-induced relaxation in rat urinary bladder smooth muscle (UBSM). BRL 37344, a specific 3-AR agonist, inhibits spontaneous contractions of isolated UBSM strips. SR59230A, a specific 3-AR antagonist, and H89, a PKA inhibitor, reduced the inhibitory effect of BRL 37344. Iberiotoxin, a specific BK channel inhibitor, shifts the BRL 37344 concentration-response curves for contraction amplitude, net muscle force, and tone to the right. Freshly dispersed UBSM cells and the perforated mode of the patch-clamp technique were used to determine further the role of 3-AR stimulation by BRL 37344 on BK channel activity. BRL 37344 increased spontaneous transient outward BK current (STOC) frequency by 46.0 ± 20.1%. In whole-cell mode at Vh = 0 mV, the single BK channel amplitude was 5.17 ± 0.28 pA, whereas in the presence of BRL 37344, it was 5.55 ± 0.41 pA. The BK channel open probability was also unchanged. In the presence of ryanodine and nifedipine, the current-voltage relationship in response to depolarization steps in the presence and absence of BRL 37344 was identical. In current-clamp mode, BRL 37344 caused membrane potential hyperpolarization from -26.1 ± 2.1 mV (control) to -29.0 ± 2.2 mV. The BRL 37344-induced hyperpolarization was eliminated by application of iberiotoxin or tetraethylammonium. The data indicate that stimulation of 3-AR relaxes rat UBSM by increasing the BK channel STOC frequency, which causes membrane hyperpolarization and thus relaxation.
