Changes in the function and expression of T-type and N-type calcium channels in the rat bladder after bladder outlet
Yasuhiko Igawa1, Shintaro Kumano2, Naoki Aizawa1
1Department of Continence Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Purpose:
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.
Materials And 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.
Insights
Bladder outlet obstruction in rats alters T-type and N-type calcium channels. Blocking these channels impacts bladder capacity and contractions, suggesting compensatory mechanisms.
Area of Science:
- Urology
- Neuroscience
- Pharmacology
Background:
- Bladder outlet obstruction (BOO) is a common condition affecting lower urinary tract function.
- Changes in ion channel activity are implicated in the pathophysiology of BOO.
- T-type and N-type calcium channels play critical roles in detrusor muscle function and afferent signaling.
Purpose of the Study:
- To investigate the functional and expressional changes of T-type and N-type calcium channels in the bladder following BOO.
- To evaluate the therapeutic potential of blocking these channels in a rat model of BOO.
Main Methods:
- Female Sprague Dawley rats underwent partial urethral ligation (BOO) or sham surgery.
- mRNA expression of T-type and N-type calcium channels was assessed in bladder, dorsal root ganglion, and spinal cord.
- In vivo cystometry and in vitro detrusor strip studies were performed using specific channel blockers.
Main Results:
- BOO led to increased mRNA expression of T-type and N-type calcium channels in the bladder and spinal cord.
- T-type channel blockade (RQ-00311610) increased bladder capacity and voided volume in obstructed rats.
- N-type channel blockade (ω-conotoxin GVIA) reduced nonvoiding contractions and suppressed specific components of detrusor contractions.
Conclusions:
- T-type calcium channel blockade enhances bladder capacity in BOO.
- N-type calcium channel blockade mitigates nonvoiding contractions in BOO.
- BOO induces compensatory upregulation of N-type calcium channels, potentially to maintain detrusor contractility via cholinergic pathways.
