Low levels of K-ATP channel activation decrease excitability and contractility of urinary bladder

Activation of ATP-sensitive potassium (K-ATP) channels can regulate smooth muscle function through membrane potential hyperpolarization. A critical is sue in understanding the role of K-ATP channels is the relationship between channel activation and the effect on tissue function. Here, we explored th is relationship in urinary bladder smooth muscle (UBSM) from the detrusor b y activating K-ATP channels with the synthetic compounds N-(4-benzoylphenyl )-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide (ZD-6169) and levcromakali m. The effects of ZD-6169 and levcromakalim on K-ATP channel currents in is olated UBSM cells, on action potentials, and on related phasic contractions of isolated UBSM strips were examined. ZD-6169 and levcromakalim at 1.02 a nd 2.63 muM, respectively, caused half-maximal activation (K-1/2) of K-ATP currents in single UBSM cells (see Heppner TJ, Bonev A, Li JH, Kau ST, and Nelson MT. Pharmacology 53: 170-179, 1996). In contrast, much lower concent rations (K-1/2 = 47 nM for ZD-6169 and K-1/2 = 38 nM for levcromakalim) cau sed inhibition of action potentials and phasic contractions of UBSM. The re sults suggest that activation of <1% of K-ATP channels is sufficient to inh ibit significantly action potentials and the related phasic contractions.