Cytosolic free magnesium modulates Na/Ca exchange currents in pig myocytes.
OBJECTIVE
Cardiac Na/Ca exchanger (NCX) protein is up-regulated and intracellular free magnesium ([Mg(2+)](i)) is significantly reduced in experimental heart failure. We asked whether changes in [Mg(2+)](i) in a physiologically relevant range could alter the I(NCX).


METHODS
The nickel-sensitive current was measured in voltage-clamped myocytes (Yorkshire pig; left ventricular) exposed to ramp pulses at 37 degrees C in Tyrode's solution containing ouabain, nifedipine and +/- Ni(2+) (5 mmol/l). The intracellular free [Ca(2+)] and [Mg(2+)] concentrations were set at 50 nmol/l and 1.25 mmol/l (HiMg) or 0.13 mmol/l (LoMg), respectively, through pipette dialysis.


RESULTS
Reducing [Mg(2+)](i) resulted in a significant increase in both outward and inward Ni-sensitive current without a shift in the reversal potential. This effect was not due to the inadvertent reduction of intracellular free [ATP] secondary to binding of ATP to Mg(2+); reducing intracellular [ATP] in LoMg cells from 1.35 mmol/l to 0.18 mmol/l did not affect I(NCX). The intracellular free [Ca(2+)] was raised from 50 to 200 nmol/l, resulting in augmented inward and outward current due to calcium activation. HiMg attenuated both inward and outward currents significantly compared to LoMg, suggesting that [Mg(2+)](i) competes with [Ca(2+)](i) at the allosteric regulatory site.


CONCLUSIONS
Cytosolic free magnesium modulates the I(NCX) over a physiologic range independent of [ATP](i). Reduced [Mg(2+)](i) in heart failure could contribute to altered calcium regulation of the NCX, contributing to the altered heart failure phenotype through enhanced NCX activity.
Wei
Shao-kui
SK
Division of Cardiology A-3060, Department of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
Quigley
John F
JF
Hanlon
Stephen U
SU
O'Rourke
Brian
B
Haigney
Mark C P
MC
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D013552:Swine
D019831:Sodium-Calcium Exchanger; D008274:Magnesium; D002118:Calcium