Differential effects of extracellular Mg2+ on thrombin-induced and capacitative Ca2+ entry in human coronary arterial endothelial cells.
Receptor-mediated and capacitative Ca2+ entry are the primary Ca2+ entry pathways in endothelial cells (ECs). The mechanisms for Ca2+ entry via these pathways have not been fully elucidated. In this study, the effect of low and high external Mg2+ concentrations on these Ca2+ entry pathways was examined in human coronary arterial ECs. External Mg2+ concentration did not affect cytosolic free Mg2+ concentration. After exposure to thrombin in Ca(2+)-free medium, addition of Ca2+ to the medium caused a rise in cytosolic free Ca2+ concentration ([Ca2+]i), indicating thrombin-induced Ca2+ influx. Thrombin-induced Ca2+ influx was inhibited by not only low but also high external Mg2+ concentrations. After depletion of endoplasmic Ca2+ stores by thapsigargin, addition of Ca2+ to the medium induced an increase in [Ca2+]i, indicating capacitative Ca2+ entry. Capacitative entry was found to be accelerated by low external Mg2+ and inhibited by high external Mg2+ concentration. Results suggest that receptor-mediated Ca2+ influx requires external Mg2+ but is inhibited by increased external Mg2+ concentrations and that capacitative Ca2+ entry is reduced by external Mg2+ in human coronary arterial ECs.
Yoshimura
M
M
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan. myoshimu@mcai.med.hiroshima-u.ac.jp
Oshima
T
T
Matsuura
H
H
Inoue
T
T
Kambe
M
M
Kajiyama
G
G
D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002451:Cell Compartmentation; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005110:Extracellular Space; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D018179:Receptors, Thrombin / Q000187:drug effects / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018179:Receptors, Thrombin; D013917:Thrombin; D008274:Magnesium; D009543:Nifedipine; D002118:Calcium