Cytosolic free magnesium modulates Na/Ca exchange currents in pig myocytes

Shao kui Wei, John F. Quigley, Stephen U. Hanlon, Brian O'Rourke, Mark C P Haigney

Research output: Contribution to journalArticle

Abstract

Objective: Cardiac Na/Ca exchanger (NCX) protein is up-regulated and intracellular free magnesium ([Mg2+]i) is significantly reduced in experimental heart failure. We asked whether changes in [Mg2+]i in a physiologically relevant range could alter the INCX. Methods: The nickel-sensitive current was measured in voltage-clamped myocytes (Yorkshire pig; left ventricular) exposed to ramp pulses at 37°C in Tyrode's solution containing ouabain, nifedipine and ±Ni2+ (5 mmol/l). The intracellular free [Ca2+] and [Mg2+] 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 [Mg2+]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 Mg2+; reducing intracellular [ATP] in LoMg cells from 1.35 mmol/l to 0.18 mmol/l did not affect INCX. The intracellular free [Ca2+] 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 [Mg2+]i competes with [Ca2+]i at the allosteric regulatory site. Conclusion: Cytosolic free magnesium modulates the INCX over a physiologic range independent of [ATP]i. Reduced [Mg2+]i in heart failure could contribute to altered calcium regulation of the NCX, contributing to the altered heart failure phenotype through enhanced NCX activity.

Original languageEnglish (US)
Pages (from-to)334-340
Number of pages7
JournalCardiovascular Research
Volume53
Issue number2
DOIs
StatePublished - 2002

Fingerprint

Muscle Cells
Magnesium
Swine
Adenosine Triphosphate
Heart Failure
Allosteric Site
Calcium
Architectural Accessibility
Ouabain
Nifedipine
Nickel
Dialysis
Phenotype
Proteins

Keywords

  • Intra/extracellular ions
  • Ion channels
  • Myocytes
  • Na/Ca-exchanger

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Cytosolic free magnesium modulates Na/Ca exchange currents in pig myocytes. / Wei, Shao kui; Quigley, John F.; Hanlon, Stephen U.; O'Rourke, Brian; Haigney, Mark C P.

In: Cardiovascular Research, Vol. 53, No. 2, 2002, p. 334-340.

Research output: Contribution to journalArticle

Wei, Shao kui ; Quigley, John F. ; Hanlon, Stephen U. ; O'Rourke, Brian ; Haigney, Mark C P. / Cytosolic free magnesium modulates Na/Ca exchange currents in pig myocytes. In: Cardiovascular Research. 2002 ; Vol. 53, No. 2. pp. 334-340.
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abstract = "Objective: Cardiac Na/Ca exchanger (NCX) protein is up-regulated and intracellular free magnesium ([Mg2+]i) is significantly reduced in experimental heart failure. We asked whether changes in [Mg2+]i in a physiologically relevant range could alter the INCX. Methods: The nickel-sensitive current was measured in voltage-clamped myocytes (Yorkshire pig; left ventricular) exposed to ramp pulses at 37°C in Tyrode's solution containing ouabain, nifedipine and ±Ni2+ (5 mmol/l). The intracellular free [Ca2+] and [Mg2+] 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 [Mg2+]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 Mg2+; reducing intracellular [ATP] in LoMg cells from 1.35 mmol/l to 0.18 mmol/l did not affect INCX. The intracellular free [Ca2+] 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 [Mg2+]i competes with [Ca2+]i at the allosteric regulatory site. Conclusion: Cytosolic free magnesium modulates the INCX over a physiologic range independent of [ATP]i. Reduced [Mg2+]i in heart failure could contribute to altered calcium regulation of the NCX, contributing to the altered heart failure phenotype through enhanced NCX activity.",
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AU - Wei, Shao kui

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AU - Hanlon, Stephen U.

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AU - Haigney, Mark C P

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AB - Objective: Cardiac Na/Ca exchanger (NCX) protein is up-regulated and intracellular free magnesium ([Mg2+]i) is significantly reduced in experimental heart failure. We asked whether changes in [Mg2+]i in a physiologically relevant range could alter the INCX. Methods: The nickel-sensitive current was measured in voltage-clamped myocytes (Yorkshire pig; left ventricular) exposed to ramp pulses at 37°C in Tyrode's solution containing ouabain, nifedipine and ±Ni2+ (5 mmol/l). The intracellular free [Ca2+] and [Mg2+] 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 [Mg2+]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 Mg2+; reducing intracellular [ATP] in LoMg cells from 1.35 mmol/l to 0.18 mmol/l did not affect INCX. The intracellular free [Ca2+] 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 [Mg2+]i competes with [Ca2+]i at the allosteric regulatory site. Conclusion: Cytosolic free magnesium modulates the INCX over a physiologic range independent of [ATP]i. Reduced [Mg2+]i in heart failure could contribute to altered calcium regulation of the NCX, contributing to the altered heart failure phenotype through enhanced NCX activity.

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