L-type Ca2+ channel function in the avian embryonic heart after cardiac neural crest ablation.
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 Ca(2+) current (I(Ca),(L)). Decreased I(Ca,L) occurs without a corresponding reduction in the alpha(1)-subunit of the Ca(2+) 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 Ca(2+) 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 (tau approximately or equal 4.5 ms) except for the sham operated at ED15 (tau = 3.4 ms). These results indicate that the cardiac neural crest influences the development of myocardial Ca(2+) channels.
Nichols
Carol A
CA
Cell Biology and Anatomy, Medical College of Georgia, Augusta, Georgia, USA.
Creazzo
Tony L
TL
D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002642:Chick Embryo; D002645:Chickens; D006321:Heart / Q000196:embryology* / Q000502:physiology*; D006330:Heart Defects, Congenital / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000502:physiology; D009432:Neural Crest / Q000196:embryology* / Q000502:physiology* / Q000601:surgery; D018408:Patch-Clamp Techniques
D020746:Calcium Channels, L-Type