title: Imaging arrhythmogenic calcium signaling in intact hearts.
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 (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.
authors.affiliation: Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, 1800 N. Capitol Ave, E475, Indianapolis, IN 46202, USA. chenpp@iupui.edu
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ogawa
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Maruyama
authors.forename: Su-Kiat
authors.initials: SK
authors.lastname: Chua
authors.forename: Po-Cheng
authors.initials: PC
authors.lastname: Chang
authors.forename: Michael
authors.initials: M
authors.lastname: Rubart-von der Lohe
authors.forename: Zhenhui
authors.initials: Z
authors.lastname: Chen
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ai
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D006321:Heart; D006352:Heart Ventricles / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D056969:Voltage-Sensitive Dye Imaging / Q000379:methods*