title: Effects of bladder outlet obstruction on properties of Ca2+-activated K+ channels in rat bladder.
abstract: In this study, we investigated the effects of bladder outlet obstruction (BOO) on the expression and function of large conductance (BK) and small conductance (SK) Ca(2+)-activated K(+) channels in detrusor smooth muscle. The bladder from adult female Sprague-Dawley rats with 6-wk BOO were used. The mRNA expression of the BK channel alpha-subunit, beta1-, beta2-, and beta4-subunits and SK1, SK2, and SK3 channels were investigated using real-time RT-PCR. All subunits except for the BK-beta2, SK2, and SK3 channels were predominantly expressed in the detrusor smooth muscle rather than in the mucosa. The mRNA expression of the BK channel alpha-subunit was not significantly changed in obstructed bladders. However, the expression of the BK channel beta1-subunit and the SK3 channel was remarkably increased in obstructed bladders. On the other hand, the expression of the BK channel beta4-subunit was decreased as the severity of BOO-induced bladder overactivity progressed. In detrusor smooth muscle strips from obstructed bladders, blockade of BK channels by iberiotoxin (IbTx) or charybdotoxin (CTx) and blockade of SK channels by apamin increased the amplitude of spontaneous contractions. These blockers also increased the contractility and affinity of these strips for carbachol during cumulative applications. The facilitatory effects elicited by these K(+) channel blockers were larger in the strips from obstructed bladders compared with control bladders. These results suggest that long-term exposure to BOO for 6 wk enhances the function of both BK and SK types of Ca(2+)-activated K(+) channels in the detrusor smooth muscle to induce an inhibition of bladder contractility, which might be a compensatory mechanism to reduce BOO-induced bladder overactivity.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, 3471 Fifth Ave., Pittsburgh, PA 15213, USA. mkita@asahikawa-med.ac.jp
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kita
authors.forename: Takakazu
authors.initials: T
authors.lastname: Yunoki
authors.forename: Koichi
authors.initials: K
authors.lastname: Takimoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyazato
authors.forename: Kaori
authors.initials: K
authors.lastname: Kita
authors.forename: William C
authors.initials: WC
authors.lastname: de Groat
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Kakizaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D005260:Female; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism / Q000503:physiopathology*; D053201:Urinary Bladder, Overactive / Q000378:metabolism / Q000503:physiopathology
chemical_list: D018679:Cholinergic Agonists; C496896:Kcnn1 protein, rat; C496899:Kcnn2 protein, rat; C496901:Kcnn3 protein, rat; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; D051640:Small-Conductance Calcium-Activated Potassium Channels; D018999:Charybdotoxin; D001030:Apamin; C064719:iberiotoxin; D002217:Carbachol