title: Changes in the function and expression of T-type and N-type calcium channels in the rat bladder after bladder outlet obstruction.
abstract: OBJECTIVE
  We evaluated possible changes in the function and expression of T-type and N-type Ca(2+) channels in the bladder of rats with bladder outlet obstruction.
  
  
  METHODS
  Female Sprague Dawley® rats were divided into a group with bladder outlet obstruction created by partial urethral ligation and a sham operated group. Six weeks postoperatively we determined the mRNA expression of T-type and N-type Ca(2+) channels in the bladder, dorsal root ganglion and spinal cord. We also cystometrically investigated expression by intravenous administration of the T-Ca blocker RQ-00311610 or the N-type Ca(2+) channel blocker ω-conotoxin GVIA. We then performed in vitro functional studies of detrusor strips using these blockers.
  
  
  RESULTS
  mRNA expression of T-type Ca(2+) channels in the bladder detrusor and mucosa layers, and the spinal cord dorsal horn, and N-type Ca(2+) channels in the whole bladder and detrusor layer, and the spinal cord dorsal horn was greater in the obstructed group than the sham operated group. In obstructed rats bladder capacity and voided volume increased after RQ-00311610 administration but the number of nonvoiding contractions decreased after ω-conotoxin GVIA administration. Detrusor strips from obstructed rats showed weaker contractile responses to electrical field stimulation, particularly in regard to the purinergic component. ω-Conotoxin GVIA suppressed electrical field stimulation induced contractions only in the detrusor of obstructed rats, especially the cholinergic component.
  
  
  CONCLUSIONS
  Blocking T-type Ca(2+) channels increased bladder capacity while N-type Ca(2+) channel blockade inhibited nonvoiding contractions in rats with bladder outlet obstruction. Decreased bladder efferent neurotransmission occurred after bladder outlet obstruction, predominantly in its purinergic component and detrusor contractions via cholinergic neurotransmission were activated in a compensatory manner, probably via N-type Ca(2+) channel up-regulation.
authors.affiliation: Department of Continence Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan. Electronic address: yigawa-jua@umin.ac.jp.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Igawa
authors.affiliation: University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kumano
authors.affiliation: Department of Continence Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Aizawa
authors.affiliation: Department of Urology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yasuho
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Continence Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ito
authors.affiliation: RaQualia Pharma, Inc., Aichi, Japan.
authors.forename: Shuzo
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: RaQualia Pharma, Inc., Aichi, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: RaQualia Pharma, Inc., Aichi, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Tajimi
authors.affiliation: Department of Urology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimatsu
authors.affiliation: Department of Urology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
mesh_terms: D000818:Animals; D020864:Calcium Channels, N-Type / Q000096:biosynthesis / Q000502:physiology*; D020747:Calcium Channels, T-Type / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000378:metabolism*; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism*
chemical_list: D020864:Calcium Channels, N-Type; D020747:Calcium Channels, T-Type
keywords: calcium channel blockers; calcium channels; electric stimulation; overactive; urinary bladder; urinary bladder neck obstruction