Regulation of SR and mitochondrial Ca 2+ signaling by L-type Ca 2+ channels and Na/Ca exchanger in hiPSC-CMs.
| Autor: | Zhang XH; Cardiac Signaling Center of USC, MUSC and Clemson University, 68 President St BEB 306, Charleston, SC 29425, USA., Morad M; Cardiac Signaling Center of USC, MUSC and Clemson University, 68 President St BEB 306, Charleston, SC 29425, USA. Electronic address: moradm@musc.edu. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Cell calcium [Cell Calcium] 2024 Dec 12; Vol. 125, pp. 102985. Date of Electronic Publication: 2024 Dec 12. |
| DOI: | 10.1016/j.ceca.2024.102985 |
| Abstrakt: | Rationale & Methods: While signaling of cardiac SR by surface membrane proteins (I Results: In voltage-clamped and TIRF-imaged cardiomyocytes, low Na + induced SR Ca 2+ release was suppressed by short pre-exposures to ∼100 nM FCCP, suggesting mitochondrial Ca 2+ contribution to low Na + triggered SR Ca 2+ release. Even though low Na + - or caffeine-triggered SR Ca 2+ release activated global mitochondrial Ca 2+ uptake, focal mitochondrial Ca 2+ signals varied in kinetics and magnitude, showing uptake or release of calcium, depending on cellular location of mitochondria. In spontaneously pacing cells, sustained caffeine exposures depleted the SR Ca 2+ content activating mitochondrial Ca 2+ uptake followed by sustained mitochondrial pacing. Spontaneous hiPSCCMs pacing was strongly suppressed by L-type calcium channels blockers, but not by inhibiting SERCA2a by CPA. Conclusion: Spontaneous hiPSCCMs pacing is triggered by influx of calcium through L-type Ca 2+ channel that gates the release of SR pools supplemented by NCX-mediated mitochondrial calcium contribution. Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors. (Copyright © 2024 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|
Full Text from ScienceDirect