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Updated: Jan 23, 2026
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A Pulmonary Trunk Banding Model of Pressure Overload Induced Right Ventricular Hypertrophy and Failure
Published on: November 29, 2018
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Knockout of the Intracellular Calcium Conducting Ion Channel Mitsugumin 23 (MG23) Protects Against Pressure Overload
Amy M Dorward1, Gavin B Robertson1, Claire Sneddon2
1School of Medicine, University of St Andrews, St Andrews, UK.
Summary
Mitsugumin 23 (MG23) channels contribute to calcium (Ca2+) leak from the sarcoplasmic reticulum, driving cardiac dysfunction. Removing MG23 protects the heart from pressure overload, reducing hypertrophy and fibrosis.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Intracellular calcium (Ca2+) dynamics are crucial for cardiac function, with disruptions leading to heart failure.
- The mechanisms behind RyR2-independent Ca2+ leak from the sarcoplasmic reticulum (SR) in cardiac dysfunction remain unclear.
- Mitsugumin 23 (MG23) is an ion channel on ER/SR and nuclear membranes, potentially involved in Ca2+ homeostasis.
Purpose of the Study:
- To investigate the role of MG23 in SR Ca2+ leak.
- To determine if MG23 knockout protects against pressure-overload induced left ventricular hypertrophy.
- To explore MG23's contribution to early-stage cardiac dysfunction.
Main Methods:
- Induction of cardiac pressure overload in wild-type (WT) and Mg23-knockout (KO) mice using Angiotensin II (AngII) infusion.
- In vivo pressure-volume dynamics measurement, Western blot for MG23 expression, and histological analysis for fibrosis and cardiomyocyte size.
- Isolation of cardiomyocytes for live-cell imaging of intracellular Ca2+ dynamics using Fluo-4 and analysis of Ca2+ spark profiles.
Main Results:
- AngII infusion increased MG23 expression in WT mouse hearts.
- Mg23-KO mice showed protection against AngII-induced cardiac hypertrophy, with reduced left ventricular fibrosis and preserved cardiac function.
- Overexpression of MG23 reduced SR Ca2+ stores, and Mg23-KO cardiomyocytes exhibited altered Ca2+ spark profiles, indicating MG23's role in SR Ca2+ leak.
Conclusions:
- MG23 plays a significant role in SR Ca2+ leak and intracellular Ca2+ dysregulation.
- Altered MG23 function contributes to the progression of pressure-overload induced cardiac dysfunction.
- Targeting MG23 may offer a therapeutic strategy for managing early-stage heart failure.
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