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08:42
Myo-mechanical Analysis of Isolated Skeletal Muscle
Published on: February 23, 2011
The sarcoplasmic reticulum and smooth muscle function: evidence from transgenic mice
R J Paul1, G E Shull, E G Kranias
1Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, OH 45267-0576, USA.
Novartis Foundation Symposium
|August 8, 2002
Summary
Transgenic mice reveal the sarcoplasmic reticulum
Area of Science:
- Physiology
- Molecular Biology
- Cardiovascular Research
Background:
- Smooth muscle calcium (Ca2+) handling is crucial for its function.
- Altering protein constituents of Ca2+ regulatory subsystems using molecular biology is a key approach.
- Transgenic mouse models offer insights into Ca2+ regulation.
Purpose of the Study:
- To review the role of the sarcoplasmic reticulum (SR) in smooth muscle Ca2+ handling.
- To emphasize the function of phospholamban (PLB) in SR regulation and smooth muscle contractility.
- To highlight findings from gene-altered mouse models.
Main Methods:
- Development of gene-targeted or gene-ablated (knockout) mice for Ca2+ regulatory proteins.
- Generation of transgenic mice for smooth muscle-specific phospholamban (PLB) expression.
- Integration of data from transgenic mouse studies with pharmacological approaches.
Main Results:
- Phospholamban (PLB) significantly modulates SR function and smooth muscle contractility.
- PLB influences both phasic and tonic smooth muscle contractility via SERCA modulation.
- Transgenic models revealed novel roles for PLB in endothelial Ca2+ homeostasis and smooth muscle relaxation.
Conclusions:
- The sarcoplasmic reticulum (SR) plays a major role in modulating smooth muscle Ca2+ and contractility.
- This modulation by the SR is tissue-specific.
- Phospholamban (PLB) is a key regulator of SR function and smooth muscle contractility.
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