It is a common sequelae of bladder outlet obstruction caused by benign prostatic hyperplasia in adult males and gives rise to significant bladder dysfunction such as frequency and urgency of micturition. The unstable detrusor contractions may lead to urge incontinence. Since it has been reported that experimentally-induced bladder instability can be abolished by ATP-sensitive K
+ channel (K
ATP channel) openers, various types of detrusor-selective K
ATP channels have been newly synthesized, targeting K
ATP channels in urinary bladder. Thus, the significant differences in molecular and pharmacological properties of K
ATP channels between urinary bladder and urethra hold out some hope for the development of tissue-selective K
ATP channel openers for urge urinary incontinence, and detrusor-selective K
ATP channel openers should be screened against urethral as well as vascular smooth muscle. In functional expression experiments, pharmacological and electrophysiological studies have reported that SUR1/Kir6.2 represents the pancreatic β-cell K
ATP channel and that SUR2A/Kir6.2 is thought to represent the cardiac K
ATP channel, whereas SUR2B/Kir6.1 represents the smooth muscle-type K
ATP channel. In general, the smooth muscle type-K
ATP channel is (i) of a relatively small conductance (about 20 pS under quasi-physiological conditions, approximately 40 pS in symmetrical 140 mM K
+ conditions), (ii) intracellular Ca
2+-insensitive, (iii) inhibited by intracellular ATP, (iv) abolished by glibenclamide at a submicromolar concentration, and (v) reactivated by intracellular nucleoside diphosphates (NDPs). There has been no report concerning the properties of K
ATP channels in human detrusor by use of single-channel recordings. We would like to introduce our recent evidence of novel synthesized detrusor-selective K
ATP channel openers and properties of K
ATP channels in the lower urinary tract.
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