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Changes in mitochondrial function induced in isolated guinea-pig ventricular myocytes by calcium overload
K K Minezaki1, M S Suleiman, R A Chapman
1British Heart Foundation Research Group, School of Veterinary Science, University of Bristol.
The Journal of Physiology
|May 1, 1994
Summary
Calcium overload in heart cells disrupts energy production by impairing mitochondrial NADH supply and causing membrane depolarization. Magnesium can mitigate these detrimental effects on cellular energy reserves.
Area of Science:
- Cardiology
- Cell Physiology
- Mitochondrial Biology
Background:
- Calcium overload is a known cause of energy depletion in cardiac myocytes.
- The precise mechanisms linking calcium overload to impaired mitochondrial function and energy loss remain incompletely understood.
Purpose of the Study:
- To investigate the dynamic changes in intracellular calcium ([Ca2+]i), pH (pHi), mitochondrial membrane potential (ψm), and mitochondrial NADH levels during calcium overload in guinea-pig ventricular myocytes.
- To elucidate the roles of mitochondrial NADH availability and membrane potential in energy depletion under calcium overload conditions.
Main Methods:
- Single isolated guinea-pig ventricular myocytes were subjected to calcium overload.
- Fluorescent techniques were employed to measure real-time changes in [Ca2+]i, pHi, ψm, and mitochondrial NADH autofluorescence.
- Experiments involved manipulating extracellular calcium and magnesium concentrations and using respiratory inhibitors/uncouplers.
Main Results:
- Calcium overload led to intracellular acidification, increased [Ca2+]i, decreased mitochondrial NADH, and sustained depolarization of ψm.
- NADH autofluorescence changes correlated with mitochondrial NADH, and depolarization of ψm was linked to impaired respiration.
- Reduced severity of calcium overload or elevated extracellular magnesium lessened these observed detrimental effects.
Conclusions:
- Energy depletion in calcium-overloaded myocytes results from both impaired citric acid cycle function (reducing mitochondrial NADH) and uncoupling of respiration due to ψm depolarization.
- Elevated intracellular sodium and calcium likely contribute to increased calcium cycling across the mitochondrial membrane, provoking ψm depolarization.
- Magnesium may play a protective role by mitigating the negative impacts of calcium overload on mitochondrial function and cellular energy status.