Regulation of Ca 2+ signaling by acute hypoxia and acidosis in cardiomyocytes derived from human induced pluripotent stem cells.

Autor: Fernández-Morales JC; Cardiac Signaling Center of MUSC, USC and Clemson, Charleston, SC, USA., Hua W; Cardiac Signaling Center of MUSC, USC and Clemson, Charleston, SC, USA., Yao Y; Cardiac Signaling Center of MUSC, USC and Clemson, Charleston, SC, USA., Morad M; Cardiac Signaling Center of MUSC, USC and Clemson, Charleston, SC, USA; Department of Pharmacology,Georgetown University Medical Center, Washington, DC, USA. Electronic address: moradm@musc.edu.
Jazyk: angličtina
Zdroj: Cell calcium [Cell Calcium] 2019 Mar; Vol. 78, pp. 1-14. Date of Electronic Publication: 2018 Dec 12.
DOI: 10.1016/j.ceca.2018.12.006
Abstrakt: Aims: The effects of acute (100 s) hypoxia and/or acidosis on Ca 2+ signaling parameters of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are explored here for the first time.
Methods and Results: 1) hiPSC-CMs express two cell populations: rapidly-inactivating I Ca myocytes (τ i <40 ms, in 4-5 day cultures) and slowly-inactivating I Cai   ≥ 40 ms, in 6-8 day cultures). 2) Hypoxia suppressed I Ca by 10-20% in rapidly- and 40-55% in slowly-inactivating I Ca cells. 3) Isoproterenol enhanced I Ca in hiPSC-CMs, but either enhanced or did not alter the hypoxic suppression. 4) Hypoxia had no differential suppressive effects in the two cell-types when Ba 2+ was the charge carrier through the calcium channels, implicating Ca 2+ -dependent inactivation in O 2 sensing. 5) Acidosis suppressed I Ca by ∼35% and ∼25% in rapidly and slowly inactivating I Ca cells, respectively. 6) Hypoxia and acidosis suppressive effects on Ca-transients depended on whether global or RyR2-microdomain were measured: with acidosis suppression was ∼25% in global and ∼37% in RyR2 Ca 2+ -microdomains in either cell type, whereas with hypoxia suppression was ∼20% and ∼25% respectively in global and RyR2-microdomaine in rapidly and ∼35% and ∼45% respectively in global and RyR2-microdomaine in slowly-inactivating cells.
Conclusions: Variability in I Ca inactivation kinetics rather than cellular ancestry seems to underlie the action potential morphology differences generally attributed to mixed atrial and ventricular cell populations in hiPSC-CMs cultures. The differential hypoxic regulation of Ca 2+ -signaling in the two-cell types arises from differential Ca 2+ -dependent inactivation of the Ca 2+ -channel caused by proximity of Ca 2+ -release stores to the Ca 2+ channels.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE