4.6 Article

Phospholamban regulation of bladder contractility: evidence from gene-altered mouse models

Journal

JOURNAL OF PHYSIOLOGY-LONDON
Volume 535, Issue 3, Pages 867-878

Publisher

WILEY
DOI: 10.1111/j.1469-7793.2001.00867.x

Keywords

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Funding

  1. NCRR NIH HHS [P40RR12358] Funding Source: Medline
  2. NHLBI NIH HHS [HL26057, HL09781, R01 HL026057, R01 HL064018, HL54829, HL25318, F32 HL009781, HL64018, R37 HL026057, R01 HL054829] Funding Source: Medline

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1. Phospholamban (PLB) is an inhibitor of the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA). Its presence and/or functional significance in contractility of bladder, a smooth muscle tissue particularly dependent on SR function, is unknown, We investigated this by measuring the effects of carbachol (CCh) on force and [Ca2+](i) in bladder from mice in which the PLB gene was ablated (PLB-KO mice). In the PLB-KO bladder, the maximum increases in [Ca2+](i) and force were significantly decreased (41.5 and 47.4 % of WT), and the EC50 values increased. 2. Inhibition of SERCA with cyclopiazonic acid (CPA) abolished these differences between WT and PLB-KO bladder, localizing the effects to the SR. 3. To determine whether these effects were specific to PLB, we generated mice with smooth-muscle-specific expression of PLB (PLB-SMOE mice), using the SMP8 alpha -actin promoter. Western blot analysis of PLB-SMOE mice showed approximately an eightfold overexpression of PLB while SERCA was downregulated 12-fold. 4. In PLB-SMOE bladders, in contrast, the response of [Ca2+](i) and force to CCh was significantly increased and the EC50 values were decreased. CPA had little affect on the CCh-induced increases in [Ca2+](i) and force in PLB-SMOE bladder. 5. These results show that alteration of the PLB:SERCA ratio can significantly modulate smooth muscle [Ca2+](i). Importantly, our data show that PLB can play a major role in modulation of bladder contractility.

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