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Intracellular calcium modulators for cardiac muscle in pathological conditions
1First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Insights
Agents stabilizing calcium release from the sarcoplasmic reticulum offer a novel approach to treating cardiac cell injury and arrhythmias caused by calcium overload. This method avoids reducing contractility, unlike previous strategies.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Excess intracellular calcium (calcium overload) is a hallmark of cardiac cell injury.
- Calcium overload leads to diastolic/systolic failure and arrhythmias, partly due to spontaneous calcium release from the sarcoplasmic reticulum.
- Prior treatments aimed at reducing intracellular calcium decreased contractility.
Purpose of the Study:
- To review agents that stabilize calcium release from the sarcoplasmic reticulum in cardiac muscle.
- To explore therapeutic strategies for calcium overload that preserve cardiac contractility.
Main Methods:
- Review of existing literature on intracellular calcium homeostasis.
- Discussion of therapeutic agents targeting sarcoplasmic reticulum calcium release.
- Focus on agents including magnesium ion, ryanodine, caffeine, dantrolene, phenytoin, R56865, KT361, and flunarizine.
Main Results:
- Agents stabilizing calcium release present a potential therapeutic avenue for cardiac dysfunction.
- This approach may circumvent the negative inotropic effects of calcium-lowering strategies.
Conclusions:
- Stabilizing sarcoplasmic reticulum calcium release is a promising strategy for managing cardiac calcium overload.
- Further research into these agents could lead to improved treatments for heart conditions.
Abstract:
This is a brief review of agents that stabilize calcium release from the sarcoplasmic reticulum in cardiac muscle. An excess intracellular calcium concentration (calcium overload) is a common feature in a variety of cardiac cell injuries. Calcium overload elicits diastolic and systolic failure, and is involved in the genesis of arrhythmias. These abnormalities appear in part to be caused by the spontaneous release of calcium ions from the sarcoplasmic reticulum. Previous efforts to treat calcium overload were made with the intention to decrease the total intracellular content of calcium ions. However, such procedures would result in a decrease in contractility. Agents that stabilized calcium release from the sarcoplasmic reticulum may therefore be useful to correct abnormalities in calcium overload. In this review, after briefly describing intracellular calcium homeostasis, strategies against calcium overload, especially those involving magnesium ion, ryanodine, caffeine, dantrolene, phenytoin, R56865, KT361 and flunarizine will be discussed.