Contribution of Na+/Ca2+ exchange current to the formation of delayed afterdepolarizations in intact rat ventricular muscle

Yoshinao Sugai, Masahito Miura, Masanori Hirose, Yuji Wakayama, Hideaki Endoh, Taichi Nishio, Jun Watanabe, Henk E.D.J. Ter Keurs, Kunio Shirato, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Aim: To evaluate the role of the Na+-Ca2+ exchange current in the induction of arrhythmias during Ca2+ waves, we investigated the relationship between Ca2+ waves and delayed afterdepolarizations (DADs) and further investigated the effect of KB-R7943, an Na+-Ca2+ exchange inhibitor, on such relationship in multicellular muscle. Methods: Force, sarcomere length, membrane potential, and [Ca2+]i dynamics were measured in 32 ventricular trabeculae from rat hearts. After the induction of Ca2+ waves by trains of electrical stimuli (400, 500, or 600 ms intervals) for 7.5 seconds, 23 Ca2+ waves in the absence of KB-R7943 and cilnidipine ([Ca 2+]o = 2.3 ± 0.2 mmol/L), 11 Ca2+ waves in the presence of 10 μmol/L KB-R7943 ([Ca2+]o = 2.5 ± 0.5 mmol/L), and 8 Ca2+ waves in the presence of 1 μmol/L cilnidipine ([Ca2+]o = 4.1 ± 0.3 mmol/L) were measured at a sarcomere length of 2.1 μm (23.9 ± 0.8°C). Results: The amplitude of DADs correlated with the velocity (r = 0.90) and the amplitude (r = 0.90) of Ca2+ waves. The amplitude of DADs was significantly decreased to ∼40% of the initial value by 10 μmol/L KB-R7943. Conclusions: These results suggest that the velocity and the amplitude of Ca2+ waves determine the formation of DADs principally through the activation of the Na+-Ca2+ exchange current, thereby inducing triggered arrhythmias in multicellular ventricular muscle.

Original languageEnglish
Pages (from-to)517-522
Number of pages6
JournalJournal of cardiovascular pharmacology
Volume53
Issue number6
DOIs
Publication statusPublished - 2009 Jun

Keywords

  • Ca waves
  • Delayed afterdepolarizations

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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