Karl-Erik Andersson led the peer-review process as the Associate Editor responsible for the paper.
T- and L-Type Voltage-Gated Calcium Channels: Their Role in Diabetic Bladder Dysfunction
Article first published online: 12 MAR 2013
© 2013 Wiley Periodicals, Inc.
Neurourology and Urodynamics
Volume 33, Issue 1, pages 147–152, January 2014
How to Cite
Jiang, X., Luttrell, I., Chitaley, K. and Yang, C. C. (2014), T- and L-Type Voltage-Gated Calcium Channels: Their Role in Diabetic Bladder Dysfunction. Neurourol. Urodyn., 33: 147–152. doi: 10.1002/nau.22391
Conflict of interest: none.
- Issue published online: 11 DEC 2013
- Article first published online: 12 MAR 2013
- Manuscript Accepted: 7 FEB 2013
- Manuscript Received: 20 MAY 2012
- William E. Bradley Family Foundation
- bladder dysfunction;
- diabetes mellitus;
- smooth muscle;
- voltage-gated calcium channel
We investigated the mechanisms of diabetic bladder dysfunction (BD) through analysis of the roles of L- and T-type voltage-gated calcium channels (VGCCs), with the ultimate goal of identifying potential drug targets for diabetic BD.
Bladder function of db/db (type 2 diabetes) and wild type (Wt) mice was evaluated by behavioral tests and in vivo cystometry. Contractile responses of bladder strips to carbachol were measured with or without pre-treatment with nifedipine (a L-type VGCC blocker) or mibefradil (a T-type VGCC blocker). Furthermore, the effects of mibefradil and nifedipine on the proliferation of human bladder smooth muscle cells (BSMCs) were studied.
db/db mice had significantly increased voiding frequency, bladder weight, bladder compliance and capacity, and heightened contractile response to carbachol, compared to Wt mice. Nifedipine, but not mibefradil, dramatically suppressed bladder tissue contraction in Wt mice. Whereas nifedipine nearly completely inhibited bladder contraction in db/db mice, mibefradil “normalized” the heightened bladder contractility of db/db mice to the level of Wt mice. In culture, mibefradil, but not nifedipine, inhibited the proliferation of human BSMCs.
Our results indicate that while L-type VGCCs play a major role in the contraction of both diabetic and non-diabetic bladders, T-type VGCCs are involved in the contraction of diabetic bladders and mediate BSMC proliferation. This study provides support for further investigations on the effect of blockade of T-type VGCC or combined blockade of both types of VGCCs in the treatment of diabetic BD. Neurourol. Urodynam. 33:147–152, 2014. © 2013 Wiley Periodicals, Inc.