Extracellular Mg2+ inhibits capacitative Ca2+ entry in vascular smooth muscle cells.
BACKGROUND
Agonist-induced Ca2+ entry is thought to be mediated by capacitative Ca2+ entry other than L-type Ca2+ channels in vascular smooth muscle cells (VSMCs). The mechanism for capacitative Ca2+ entry has not been fully elucidated. Our objective was to examine the effect of external Mg2+ on capacitative Ca2+ entry in cultured rat aortic VSMCs.


RESULTS
Three doses of external Mg2+ concentration (nominally 0, 1, and 5 mmol/L) were used. After exposure to 1 mumol/L, angiotensin II (Ang II) in Ca(2+)-free medium, addition of Ca2+ to the medium caused an increase in cytosolic free Ca2+ concentration ([Ca2+]i), indicating Ang II-induced Ca2+ influx. This Ca2+ influx was attenuated in cells preincubated with high external Mg2+ concentrations or with 1 mumol/L nifedipine. After VSMCs in Ca(2+)-free medium were exposed to 1 mumol/L thapsigargin, which inhibits the sarcoplasmic reticulum Ca(2+)-ATPase and depletes Ca2+ stores, addition of Ca2+ to the medium induced an increase in [Ca2+]i, indicating capacitative Ca2+ entry. This entry pathway was found to be independent of dihydropyridine-sensitive Ca2+ channels and inhibited by increased external Mg2+ concentration. External Mg2+ concentration did not influence Ca2+ efflux across the plasma membrane after stimulation with Ang II plus thapsigargin.


CONCLUSIONS
Results suggest that in VSMCs, capacitative Ca2+ entry is reduced by external Mg2+. This mechanism may explain in part the inhibitory effect of external Mg2+ on Ca2+ handling.
Yoshimura
M
M
First Department of Internal Medicine, Hiroshima (Japan) University School of Medicine.
Oshima
T
T
Matsuura
H
H
Ishida
T
T
Kambe
M
M
Kajiyama
G
G
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology
D015220:Calcium Channels; D000804:Angiotensin II; D019284:Thapsigargin; D008274:Magnesium; D009543:Nifedipine; D002118:Calcium