This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 99/7/E65    most recent 01.RES.0000244087.36230.bfv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aistrup, G. L. Articles by Wasserstrom, J. A. Search for Related Content PubMed PubMed Citation Articles by Aistrup, G. L. Articles by Wasserstrom, J. A. Related Collections Calcium cycling/excitation-contraction coupling Cell signalling/signal transduction

(Circulation Research. 2006;99:E65.)
© 2006 American Heart Association, Inc.

UltraRapid Communications

Pacing-induced Heterogeneities in Intracellular Ca²⁺ Signaling, Cardiac Alternans, and Ventricular Arrhythmias in Intact Rat Heart

Gary L. Aistrup, James E. Kelly, Sunil Kapur, Michael Kowalczyk, Inbal Sysman-Wolpin, Alan H. Kadish, J. Andrew Wasserstrom

From the Departments of Molecular Pharmacology (G.L.A., J.A.W.), Biological Chemistry (G.L.A., J.A.W.), and Medicine (Division of Cardiology) (J.E.K., S.K., M.K., I.S.-W., A.H.K., J.A.W.) and The Feinberg Cardiovascular Research Institute (A.H.K., J.A.W.), Northwestern University Feinberg School of Medicine, Chicago, Ill.

Correspondence to J. Andrew Wasserstrom, Division of Cardiology (S203) Ward 3-105, 303 E Chicago Ave, Chicago, IL 60611. E-mail ja-wasserstrom{at}northwestern.edu

Optical mapping studies have suggested that intracellular Ca²⁺ and T-wave alternans are linked through underlying alternations in Ca²⁺ cycling-inducing oscillations in action potential duration through Ca²⁺-sensitive conductances. However, these studies cannot measure single-cell behavior; therefore, the Ca²⁺ cycling heterogeneities within microscopic ventricular regions are unknown. The goal of this study was to measure cellular activity in intact myocardium during rapid pacing and arrhythmias. We used single-photon laser-scanning confocal microscopy to measure Ca²⁺ signaling in individual myocytes of intact rat myocardium during rapid pacing and during pacing-induced ventricular arrhythmias. At low rates, all myocytes demonstrate Ca²⁺ alternans that is synchronized but whose magnitude varies depending on recovery kinetics of Ca²⁺ cycling for each individual myocyte. As rate increases, some cells reverse alternans phase, giving a dyssynchronous activation pattern, even in adjoining myocytes. Increased pacing rate also induces subcellular alternans where Ca²⁺ alternates out of phase with different regions within the same cell. These forms of heterogeneous Ca²⁺ signaling also occurred during pacing-induced ventricular tachycardia. Our results demonstrate highly nonuniform Ca²⁺ signaling among and within individual myocytes in intact heart during rapid pacing and arrhythmias. Thus, certain pathophysiological conditions that alter Ca²⁺ cycling kinetics, such as heart failure, might promote ventricular arrhythmias by exaggerating these cellular heterogeneities in Ca²⁺ signaling.

Key Words: calcium transients • calcium alternans • subcellular alternans • arrhythmias

This article has been cited by other articles:

				Y. Li, M. E. Diaz, D. A. Eisner, and S. O'Neill The effects of membrane potential, SR Ca2+ content and RyR responsiveness on systolic Ca2+ alternans in rat ventricular myocytes J. Physiol., March 15, 2009; 587(6): 1283 - 1292. [Abstract] [Full Text] [PDF]