Gender influences [Ca(2+)](i) during metabolic inhibition in myocytes overexpressing the Na(+)-Ca(2+) exchanger.
BACKGROUND
The Na(+)-Ca(2+) exchanger (NCX) may contribute to Ca(2+) overload and injury in ischemic cardiomyocytes. Recently, NCX overexpression was reported to increase ischemia/reperfusion injury in male and oophorectomized female but not in female mice. We therefore measured the effects of gender and estrogen on [Ca(2+)](i) and [Na(+)](i) during metabolic inhibition (MI) in myocytes from wild-type (WT) and transgenic (TG) mice overexpressing NCX.


RESULTS
Flow cytometry was used with fluo 3 for [Ca(2+)](i) and sodium green for [Na(+)](i) measurements. Male TG mouse myocytes had higher [Ca(2+)](i) after 30 minutes of MI (1086+/-160 nmol/L, n=8) than male WT (688+/-104 nmol/L, n=9, P=0.01). The increase in [Ca(2+)](i) during MI induced by NCX overexpression in female myocytes was not significant, however (TG 552+/-62 nmol/L, n=9; WT 426+/-44 nmol/L, n=7). The magnitude of rise in [Ca(2+)](i) during MI was greater in male than female myocytes. KB-R7943, an NCX inhibitor, abolished the effect of NCX overexpression but did not totally eliminate the effect of gender on [Ca(2+)](i) during MI. NCX current density and basal Na(+) pump function were not influenced by gender. The rise in [Na(+)](i) during MI was greater in male than in female myocytes. Estrogen attenuated the increase in [Ca(2+)](i) and [Na(+)](i) in male myocytes during MI and abolished the gender difference in [Na(+)](i) during MI.


CONCLUSIONS
Increased expression of NCX results in a more marked rise in [Ca(2+)](i) during MI in male than in female mouse myocytes. This gender difference appears to be mediated in part by an inhibitory effect of estrogen on the rise in [Na(+)](i), an NCX modifier, during MI.
Sugishita
K
K
Division of Cardiology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
Su
Z
Z
Li
F
F
Philipson
K D
KD
Barry
W H
WH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D015870:Gene Expression; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007424:Intracellular Fluid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012737:Sex Factors; D012964:Sodium / Q000378:metabolism; D012966:Sodium Cyanide / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D005456:Fluorescent Dyes; D019831:Sodium-Calcium Exchanger; D004958:Estradiol; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D013890:Thiourea; D012966:Sodium Cyanide; D002118:Calcium