Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) enhances triggered afterdepolarizations in rat ventricular myocytes

An Xie, Nigel J. Walker, Desuo Wang

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on action potential and afterdepolarizations were studied in rat ventricular myocytes using nystatin-perforated whole-cell patch-clamp technique. TCDD treatment, in the concentration range of 1 to 100 nM, significantly prolonged action potential duration measured at 90% of repolarization (APD90). The triggered delayedafterdepolarizations (DADs) were observed in 6 out of 8 cells after exposure of TCDD (10 nM). In the presence of isoproterenol (ISO, 10 nM) or Bay K 8644 (1 μM), TCDD (10 nM) markedly augmented the amplitude and frequency of the arrhythmogenic DADs and triggered sustained spontaneous firings in ventricular myocytes. Voltage-clamp data indicated that TCDD (10 nM) exposure significantly enhanced the transient inward current (Iti). The triggered earlyafterdepolarizations (EADs) were evoked only in cells simultaneously exposed to TCDD (10 nM) and ISO (or Bay K 8644). Further study indicated that TCDD treatment increased L-type Ca2+ current. These results indicate that activation of TCDD signaling pathway can prolong action potential duration and cause abnormal triggered afterdepolarizations. These effects may lead to clinically relevant ventricular arrhythmia especially when susceptible individuals are under elevated sympathetic stress or suffering from other myocardiopathies coincided with Ca2+-overload.

Original languageEnglish (US)
Pages (from-to)99-110
Number of pages12
JournalCardiovascular Toxicology
Volume6
Issue number2
DOIs
StatePublished - Jun 2006
Externally publishedYes

Bibliographical note

Funding Information:
The study was supported by TIP grant from NIEHS/ NIH (5 K22 ES00367). NJW is supported by the Intramural Research Program of the NIEHS, NIH.

Keywords

  • Afterdepolarizations
  • Cardiac action potential
  • TCDD
  • Transient outward current
  • Triggered activity
  • Ventricular arrhythmia

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