Evidence for mitochondrial Ca(2+)-induced Ca2+ release in permeabilised endothelial cells

Area of Science:

• Cellular Physiology
• Mitochondrial Biology
• Calcium Signaling

Background:

• Intracellular calcium (Ca2+) is primarily stored in the endoplasmic reticulum (ER) and mitochondria.
• A mitochondrial Ca2+-induced Ca2+ release (mCICR) mechanism, independent of ryanodine receptors (RyRs), has been identified in tumor cells.
• The presence and mechanism of mCICR in BAE cells remained uncharacterized.

Purpose of the Study:

• To investigate the existence and mechanism of mitochondrial Ca2+ release in BAE cells.
• To determine if the previously reported ryanodine-caffeine insensitive Ca2+ induced Ca2+ release (CICR) in BAE cells involves mitochondria.

Main Methods:

• Utilized saponin-permeabilized BAE cells to study Ca2+ signaling.
• Applied mitochondrial inhibitors (CN, FCCP, RR) and an ER Ca2+-ATPase inhibitor (thapsigargin).
• Investigated the role of the mitochondrial permeability transition pore (PTP) using cyclosporin A.

Main Results:

• Mitochondrial inhibitors significantly reduced total CICR by approximately 25%.
• The ER Ca2+-ATPase inhibitor thapsigargin had no effect on total CICR.
• Cyclosporin A, a PTP inhibitor, abolished total CICR, indicating PTP involvement.

Conclusions:

• The novel ryanodine-caffeine insensitive CICR in BAE cells involves mitochondrial Ca2+ release.
• Mitochondrial Ca2+ release in BAE cells occurs via the mitochondrial permeability transition pore (PTP).
• This mCICR mechanism may play a significant role in endothelial cell Ca2+ signaling.