Large conductance voltage‐ and Ca 2+ ‐activated K + (BK) channels mediate the β‐adrenergic relaxation of mouse urinary bladder smooth muscle

In urinary bladder smooth muscle (UBSM), stimulation of β‐adrenergic receptors (βAR) leads to activation of BK channels (Petkov & Nelson, Am. J. Physiol ., 2005, 288(6): C1255–63). Here we tested the hypothesis that the BK channel mediates the UBSM relaxation in response to βAR stimulation using the specific BK channel inhibitor, iberiotoxin (IBTX) and BK channel knockout (BK‐KO) mouse model in which the gene for the pore‐forming subunit was deleted. UBSM strips isolated from wild type (WT) and BK‐KO mice were stimulated with 20 mM K + or 1 μM carbachol to induce phasic and tonic contractions. BK‐KO UBSM and WT UBSM strips pretreated with IBTX had increased overall contractility. Isoproterenol, a non‐specific βAR agonist, as well as forskolin, an adenylate cyclase activator, decreased phasic and tonic contractions of WT UBSM strips in a concentration dependent manner. In the presence of IBTX, the concentration response curves to isoproterenol and forskolin were shifted to the right in WT UBSM strips. Surprisingly, isoproterenol‐ and forskolin‐mediated relaxations were paradoxically enhanced in BK‐KO UBSM strips and a leftward shift in the concentration response curves was observed, suggesting up‐regulation of the βAR‐cAMP pathway in BK‐KO mouse. Collectively, these results support the concept that the BK channel has a central role in βAR‐mediated relaxations of UBSM. Supported by NIH DK070909.