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This Article Full Text Full Text (PDF) Supplemental Video All Versions of this Article: 294/1/H433    most recent 01165.2007v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by de Diego, C. Articles by Valderrábano, M. Search for Related Content PubMed PubMed Citation Articles by de Diego, C. Articles by Valderrábano, M.

Cardiac alternans in embryonic mouse ventricles

Cardiovascular Research Laboratory, Departments of Medicine (Cardiology) and Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California

Submitted 8 October 2007 ; accepted in final form 7 November 2007

T-wave alternans, an important arrhythmogenic factor, has recently been described in human fetuses. Here we sought to determine whether alternans can be induced in the embryonic mouse hearts, despite its underdeveloped sarcoplasmic reticulum (SR) and, if so, to analyze the response to pharmacological and autonomic interventions. Immunohistochemistry confirmed minimal sarcoplasmic-endoplasmic reticulum Ca-ATPase 2a expression in embryonic mouse hearts at embryonic day (E) 10.5 to E12.5, compared with neonatal or adult mouse hearts. We optically mapped voltage and/or intracellular Ca (Ca_i) in 99 embryonic mouse hearts (dual mapping in 64 hearts) at these ages. Under control conditions, ventricular action potential duration (APD) and Ca_i transient alternans occurred during rapid pacing at an average cycle length of 212 ± 34 ms in 57% (n = 15/26) of E10.5-E12.5 hearts. Maximum APD restitution slope was steeper in hearts developing alternans than those that did not (2.2 ± 0.6 vs. 0.8 ± 0.4; P < 0.001). Disabling SR Ca_i cycling with thapsigargin plus ryanodine did not significantly reduce alternans incidence (44%, n = 8/18, P = 0.5), whereas isoproterenol (n = 14) increased the incidence to 100% (P < 0.05), coincident with steepening APD restitution slope. Verapamil abolished Ca_i transients (n = 9). Thapsigargin plus ryanodine had no major effects on Ca_i-transient amplitude or its half time of recovery in E10.5 hearts, but significantly depressed Ca_i-transient amplitude (by 47 ± 8%) and prolonged its half time of recovery (by 18 ± 3%) in E11.5 and older hearts. Embryonic mouse ventricles can develop cardiac alternans, which generally is well correlated with APD restitution slope and does not depend on fully functional SR Ca_i cycling.

calcium cycling; cardiac development