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Published on: February 15, 2022
Ca2+ clearance and contractility in vascular smooth muscle: evidence from gene-altered murine models
Brian Oloizia1, Richard J Paul
1Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0576, USA.
Insights
Calcium clearance proteins are vital for heart muscle function. Recent studies using gene-modified mice reveal their crucial roles in vascular smooth muscle contractility, suggesting potential links to smooth muscle diseases.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Muscle Physiology
Background:
- Calcium (Ca2+) handling proteins are critical for myocardial contractility and intracellular Ca2+ levels.
- Key proteins include the Na+-Ca2+ exchanger, Na+-K+ ATPase, and SERCA/phospholamban.
- Their roles in vascular smooth muscle are less understood compared to cardiomyocytes.
Purpose of the Study:
- To review Ca2+ clearance mechanisms in smooth muscle.
- To compare Ca2+ handling in smooth muscle and cardiomyocytes using gene-modified mouse models.
- To explore the implications of phospholamban mutations in smooth muscle.
Main Methods:
- Review of studies utilizing gene-targeted and transgenic mouse models.
- Comparison of findings in vascular smooth muscle with those in cardiomyocytes.
- Analysis of human phospholamban mutations.
Main Results:
- Gene-modified mouse models have significantly advanced understanding of Ca2+ clearance proteins in smooth muscle.
- These proteins regulate both tonic and phasic smooth muscle contractility.
- Phospholamban mutations linked to dilated cardiomyopathy are also found in smooth muscle.
Conclusions:
- Ca2+ clearance systems are essential for smooth muscle function.
- Further research into Ca2+ handling in smooth muscle is warranted.
- Mutations in Ca2+ clearance proteins may lead to smooth muscle pathologies.
Abstract:
The central importance of calcium clearance proteins, and their regulators, in the modulation of myocardial contractility and intracellular Ca(2+) concentration ([Ca(2+)](i)) has long been established. Key players identified include the Na(+)-Ca(2+) exchanger, the Na(+)-K(+) ATPase, the sarco(endo)plasmic reticulum Ca(2+)-ATPase and associated phospholamban. Gene-targeted and transgenic murine models have been critical in the elucidation of their function. The study of these proteins in the regulation of contractile parameters in vascular smooth muscle, on the other hand, is less well studied. More recently, gene-targeted and transgenic models have expanded our knowledge of Ca(2+) clearance proteins and their role in both tonic and phasic smooth muscle contractility. In this review, we will briefly treat the mechanisms which underlie Ca(2+) clearance in smooth muscle. These will be addressed in light of studies using gene-modified mouse models, the results of which will be compared and contrasted with those in the cardiomyocyte. The recently identified human mutations in phospholamban, which lead to dilated cardiomyopathy, are also present in vascular and other smooth muscle. Given the importance of these Ca(2+) clearance systems to modulation of smooth muscle, it is likely that mutations will also lead to smooth muscle pathology.
