Beta-adrenergic stimulation of pig myocytes with decreased cytosolic free magnesium prolongs the action potential and enhances triggered activity

Shao Kui Wei, Stephen U. Hanlon, Mark C.P. Haigney*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Introduction: Heart failure results in chronic beta-adrenergic stimulation, repolarization lability, and arrhythmias associated with early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs). Having described a significant reduction in intracellular free magnesium ([Mg2+]i) in experimental heart failure, we asked whether a reduction in [Mg2+]i would delay repolarization or facilitate EADs and/or DADs. Methods and Results: Left ventricular myocytes were isolated from Yorkshire swine. Cytosolic free [Mg2+] was set at 0.12 mM (LoMg) or 1.2 mM (HiMg) through pipette dialysis. Action potentials (AP), Ca current (ICa), and sodium/calcium exchange current (INCX) were measured in the presence or absence of isoproterenol (2 μM) at 37°C. Under basal conditions (0.1-Hz stimulation, 2 mM external [Ca2+]), reducing [Mg2+]i had no effect on AP duration and ICa but did significantly enhance INCX. In contrast, during superfusion with isoproterenol, reduced [Mg2+]i caused a significant increase in AP duration at both 50% and 90% repolarization (APD50 and APD90) compared with HiMg (P < 0.05). LoMg cells manifested a high incidence of triggered activities, including spontaneous AP, EADs, and DADs (83.3% in LoMg, n = 12 vs 38.3% in HiMg, n = 13; P < 0.05). ICa and INCX were significantly increased in LoMg cells compared with HiMg cells (P < 0.05). Conclusion: Decreased cytosolic free magnesium prolongs AP duration and increases the incidence of triggered activity during beta-adrenergic stimulation. These effects may be due to increased ICa and INCX in the presence of reduced intracellular [Mg2+]. A magnesium-dependent increase in triggered activity coupled with delayed repolarization during beta-adrenergic stimulation could contribute to the arrhythmogenic substrate in heart failure.

Original languageEnglish
Pages (from-to)587-592
Number of pages6
JournalJournal of Cardiovascular Electrophysiology
Issue number6
StatePublished - 2002
Externally publishedYes


  • Beta-adrenergic stimulation
  • Calcium current
  • Delayed afterdepolarization
  • Early afterdepolarization
  • Magnesium
  • Sodium/calcium exchange current


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