title: Partial bladder outlet obstruction is associated with decreased expression and function of the small-conductance Ca2+-activated K+channel in guinea pig detrusor smooth muscle.
abstract: OBJECTIVE
  Partial bladder outlet obstruction (PBOO) usually induces overactive bladder (OAB) associated with detrusor overactivity (DO) which is related to the increased contractility of detrusor smooth muscle (DSM). The pharmacological activation of small-conductance Ca2+-activated K+(SK) channels dramatically attenuates DSM contractility. However, the role of SK channels in the PBOO DSM is less clear. Here, we tested the hypothesis that PBOO is associated with decreased expression and function of SK channels in DSM and that the activation of SK channels is a potential target to regulate DO.
  
  
  METHODS
  Two weeks after surgically inducing PBOO in female guinea pigs, cystometry indicated that DO was achieved. Using this animal model, we conducted quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and isometric tension recordings.
  
  
  RESULTS
  The qRT-PCR experiments indicated that PBOO DSM had reduced SK channel mRNA expression. Isometric tension recordings showed a decreased inhibitory effect of NS309 on spontaneous phasic and electrical field stimulation-induced contractions via the activation of SK channels in PBOO DSM.
  
  
  CONCLUSIONS
  This study presents the novel finding that PBOO is associated with attenuated DSM SK channel expression and function, which results in increased DSM contractility and contributes to DO. Therefore, SK channels could be a therapeutic target to control OAB.
authors.affiliation: Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Stomatology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China.
authors.forename: Zizheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China. pingwang-cmu@hotmail.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D010091:Oximes / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics* / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000150:complications; D053201:Urinary Bladder, Overactive / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D014563:Urodynamics
chemical_list: C493327:6,7-dichloro-1H-indole-2,3-dione 3-oxime; D007211:Indoles; D010091:Oximes; D011720:Pyrazoles; D012333:RNA, Messenger; D051640:Small-Conductance Calcium-Activated Potassium Channels; C411671:TRAM 34; D001030:Apamin
keywords: NS309; Partial bladder outlet obstruction; SK channel