T- and L-type voltage-gated calcium channels: their role in diabetic bladder dysfunction
Xiaogang Jiang1, Ian Luttrell, Kanchan Chitaley
1Department of Urology, University of Washington, Seattle, Washington.
Neurourology and Urodynamics
|March 16, 2013
Summary
Diabetic bladder dysfunction involves T-type calcium channels, which also drive cell growth. Blocking these channels may treat diabetic bladder issues.
Area of Science:
- Urology
- Pharmacology
- Diabetology
Background:
- Diabetic bladder dysfunction (BD) is a common complication of diabetes.
- Voltage-gated calcium channels (VGCCs) play a role in bladder smooth muscle function.
Purpose of the Study:
- To investigate the roles of L-type and T-type VGCCs in diabetic bladder dysfunction.
- To identify potential therapeutic targets for diabetic BD.
Main Methods:
- Comparison of bladder function in diabetic (db/db) and wild-type (Wt) mice.
- Assessment of bladder strip contractility with L-type (nifedipine) and T-type (mibefradil) VGCC blockers.
- Evaluation of VGCC blocker effects on human bladder smooth muscle cell (BSMC) proliferation.
Main Results:
- Diabetic mice exhibited increased voiding frequency, bladder weight, compliance, capacity, and carbachol-induced contraction.
- L-type VGCCs were crucial for bladder contraction in both Wt and diabetic mice.
- T-type VGCCs normalized heightened contractility in diabetic bladders and inhibited BSMC proliferation.
Conclusions:
- L-type VGCCs are essential for bladder contraction, while T-type VGCCs contribute to diabetic bladder contraction and BSMC proliferation.
- T-type VGCC blockade, or combined blockade, shows promise for treating diabetic BD.
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