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Imaging Arrhythmogenic Calcium Signaling in Intact Hearts

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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 (V m) and Cai transient in Langendorff-perfused rabbit ventricles to better define the mechanisms by which V m 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 (I KAS) 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 I KAS may be a novel antiarrhythmic targets in patients with heart failure and electrical storms.

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Acknowledgment

This study was supported in part by National Institutes of Health Grants no. P01 HL78931, R01 HL78932, and HL71140 as well as a Medtronic-Zipes endowment.

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Authors and Affiliations

  1. Krannert Institute of Cardiology and the Division of Cardiology, Department of Medicine, Indiana University School of Medicine, 1800N. Capitol Ave, E475, Indianapolis, IN, 46202, USA

    Peng-Sheng Chen, Po-Cheng Chang, Zhenhui Chen, Tomohiko Ai & Shien-Fong Lin

  2. Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan

    Masahiro Ogawa

  3. Cardiovascular Center, Chiba-Hokusoh Hospital, Nippon Medical School, Chiba, Japan

    Mitsunori Maruyama

  4. Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

    Su-Kiat Chua

  5. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA

    Michael Rubart-von der Lohe

Authors
  1. Peng-Sheng Chen
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  2. Masahiro Ogawa
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  3. Mitsunori Maruyama
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  4. Su-Kiat Chua
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  5. Po-Cheng Chang
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  6. Michael Rubart-von der Lohe
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  7. Zhenhui Chen
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  8. Tomohiko Ai
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  9. Shien-Fong Lin
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Correspondence to Peng-Sheng Chen.

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Chen, PS., Ogawa, M., Maruyama, M. et al. Imaging Arrhythmogenic Calcium Signaling in Intact Hearts. Pediatr Cardiol 33, 968–974 (2012). https://doi.org/10.1007/s00246-012-0236-5

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  • DOI: https://doi.org/10.1007/s00246-012-0236-5

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