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This Article Full Text Full Text (PDF) All Versions of this Article: 288/3/H1173    most recent 00792.2004v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Nichols, C. A. Articles by Creazzo, T. L. Search for Related Content PubMed PubMed Citation Articles by Nichols, C. A. Articles by Creazzo, T. L.

L-type Ca²⁺ channel function in the avian embryonic heart after cardiac neural crest ablation

¹Cell Biology and Anatomy, Medical College of Georgia, Augusta, Georgia; and ²Pediatrics/Neonatology Division, Neonatal/Perinatal Research Institute, Duke University Medical Center, Durham, North Carolina

Submitted 4 August 2004 ; accepted in final form 4 November 2004

In avian and mammalian embryos, surgical ablation or severely reduced migration of the cardiac neural crest leads to a failure of outflow tract septation known as persistent truncus arteriosus (PTA) and leads to embryo lethality due partly to impaired excitation-contraction coupling stemming primarily from a reduction in the L-type Ca²⁺ current (I_Ca,_L). Decreased I_Ca,L occurs without a corresponding reduction in the ₁-subunit of the Ca²⁺ channel. We hypothesize that decreased I_Ca,_L is due to reduced function at the single channel level. The cell-attached patch clamp with Na⁺ as the charge carrier was used to examine single Ca²⁺ channel activity in myocytes from normal hearts from sham-operated embryos and from hearts diagnosed with PTA at embryonic days (ED) 11 and 15 after laser ablation of the cardiac neural crest. In normal hearts, the number of single channel events per 200-ms depolarization and the mean open channel probability (P_o) was 1.89 ± 0.17 and 0.067 ± 0.008 for ED11 and 1.14 ± 0.17 and 0.044 ± 0.005 for ED15, respectively. These values represent a normal reduction in channel function and I_Ca,_L observed with development. However, the number of single channel events was significantly reduced in hearts with PTA at both ED11 and ED15 (71% and 47%, respectively) with a corresponding reduction in P_o (75% and 43%). The open time frequency histograms were best fitted by single exponentials with similar decay constants ( 4.5 ms) except for the sham operated at ED15 ( = 3.4 ms). These results indicate that the cardiac neural crest influences the development of myocardial Ca²⁺ channels.

heart development; heart defect; excitation-contraction coupling