Cardiac alternans in embryonic mouse ventricles

Carlos De Diego, Fuhua Chen, Lai Hua Xie, Amish S. Dave, Mya Thu, Christine Rongey, James N. Weiss, Miguel Valderrábano

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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 (Cai) 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 Cai 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 Cai 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 Cai-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 Cai cycling.

Original languageEnglish (US)
Pages (from-to)H433-H440
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume294
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Calcium cycling
  • Cardiac development

ASJC Scopus subject areas

  • Physiology

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