Changes in mitochondrial calcium concentration during the cardiac contraction cycle

Area of Science:

• Cardiovascular Physiology
• Mitochondrial Biology
• Cellular Electrophysiology

Background:

• Mitochondria play a crucial role in cellular calcium homeostasis.
• Understanding mitochondrial calcium handling is vital for comprehending cardiac function and dysfunction.

Purpose of the Study:

• To determine if mitochondrial calcium (Ca2+) fluxes are sufficient to alter mitochondrial and cytosolic calcium concentrations during the cardiac contraction cycle.
• To quantify mitochondrial Ca2+ uptake and release rates during systole and diastole.

Main Methods:

• Isolated guinea pig ventricular myocytes were subjected to electrical stimulation to induce contractions.
• Electron-probe microanalysis was used to measure mitochondrial and cytosolic calcium concentrations at specific points in the contraction cycle.
• Experiments involving DNP (2,4-dinitrophenol) and FCCP (carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone) evaluated mitochondrial Ca2+ uptake.

Main Results:

• Mitochondrial calcium content significantly increased during systole, peaking at 1050 mumol/L approximately 40 ms after systole onset.
• Estimated net mitochondrial Ca2+ influx was 100 nmol/s/mg protein, and efflux was 36 nmol/s/mg protein.
• Changes in mitochondrial calcium correlated with shifts in mitochondrial chloride and potassium, suggesting Ca2+-activated channel activity.

Conclusions:

• Mitochondrial calcium content undergoes substantial changes within each cardiac contraction cycle.
• Significant calcium uptake occurs during systole, with subsequent release during late systole and diastole.
• These dynamic mitochondrial calcium fluxes are integral to the regulation of cellular calcium during heart muscle activity.