Phospholamban regulation of bladder contractility: evidence from gene‐altered mouse models
Year: 2001
Type: article
Abstract: 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.
Source: The Journal of Physiology
Institution: University of Cincinnati
Language: English
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1073661697, G1276932499, G1492606380, PHOSPHOLAMBAN AND RESISTANCE VESSEL FUNCTION, G2740653044, Calcium Handling in Cardiac Pathophysiology, G3900402071, TARGETED ABLATION AND ALTERATION OF PHOSPHOLAMBAN, PHOSPHOLAMBAN MODULATION OF SMOOTH MUSCLE CONTRACTILITY, TRANSGENIC MICE WITH ALTERED CALCIUM HANDLING, Cardiac Sarcoplasmic Reticulum Calcium Cycling Proteins, G950845914
OpenAlex ID: W1988165477