Imaging arrhythmogenic calcium signaling in intact hearts

Peng Sheng Chen, Masahiro Ogawa, Mitsunori Maruyama, Su Kiat Chua, Po Cheng Chang, Michael Rubart-Von Der Lohe, Zhenhui Chen, Tomohiko Ai, Shien Fong Lin

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Protein complex of the cardiac junctional sarcoplasmic reticulum (SR) membrane formed by type 2 ryanodine receptor, junction, triadin, and calsequestrin is responsible for controlling SR calcium (Ca) release. Increased intracellular calcium (Cai) activates the electrogenic sodium-Ca exchanger current, which is known to be important in afterdepolarization and triggered activities (TAs). Using optical-mapping techniques, it is possible to simultaneously map membrane potential (Vm) and Cai transient in Langendorff-perfused rabbit ventricles to better define the mechanisms by which Vm and Cai interactions cause early afterdepolarizations (EADs). Phase 3 EAD is dependent on heterogeneously prolonged action potential duration (APD). Electrotonic currents that flow between a persistently depolarized region and its recovered neighbors underlies the mechanisms of phase 3 EADs and TAs. In contrast, "late phase-3 EAD" is induced by APD shortening, not APD prolongation. In failing ventricles, upregulation of apamin-sensitive Ca-activated potassium (K) channels (IKAS) causes APD shortening after fibrillation- defibrillation episodes. Shortened APD in the presence of large Cai transients generates late-phase 3 EADs and recurrent spontaneous ventricular fibrillation. The latter findings suggest that IKAS may be a novel antiarrhythmic targets in patients with heart failure and electrical storms.

Original languageEnglish (US)
Pages (from-to)968-974
Number of pages7
JournalPediatric Cardiology
Volume33
Issue number6
DOIs
StatePublished - Aug 2012

Keywords

  • After depolarization
  • Calcium dynamics
  • Optical mapping
  • Triggered activity
  • Ventricular fibrillation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pediatrics, Perinatology, and Child Health

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