Imaging Arrhythmogenic Calcium Signaling in Intact Hearts

• Published in: Pediatric cardiology 2012-08, Vol.33 (6), p.968-974
• Main Authors: Chen, Peng-Sheng, Ogawa, Masahiro, Maruyama, Mitsunori, Chua, Su-Kiat, Chang, Po-Cheng, Rubart-von der Lohe, Michael, Chen, Zhenhui, Ai, Tomohiko, Lin, Shien-Fong
• Format: Article
• Language: English
• Subjects: Animals; Anti-arrhythmia drugs; Arrhythmias, Cardiac - metabolism; Calcium Signaling - physiology; Calcium-binding proteins; Cardiac patients; Cardiac Surgery; Cardiology; Heart; Heart Ventricles - metabolism; Medicine; Medicine & Public Health; Myocytes, Cardiac - metabolism; Rabbits; Riley Symposium; Sarcoplasmic Reticulum - metabolism; Vascular Surgery; Voltage-Sensitive Dye Imaging - methods
• ISSN: 0172-0643; 1432-1971
• DOI: 10.1007/s00246-012-0236-5

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 (Ca i ) 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 Ca i transient in Langendorff-perfused rabbit ventricles to better define the mechanisms by which V m and Ca i 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 Ca i 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.