Excitation-contraction coupling in the day 15 embryonic chick heart with persistent truncus arteriosus.
Ca2+ transients were examined in embryonic chick hearts with an experimentally induced cardiac neural crest-related outflow tract defect known as persistent truncus arteriosus (PTA). In all of the animal models of neural crest-related heart defects, prenatal mortality is too high to be attributed to structural defects of the heart alone, suggesting that there is altered development of the myocardium. Earlier reports indicating reduced L-type Ca2+ current in hearts with PTA suggest that poor viability may be related to impairment of cardiac excitation-contraction coupling. To test this hypothesis, direct measurements of the systolic Ca2+ transient in fura-2-loaded myocytes from normal hearts and hearts with PTA were carried out. We found that Ca2+ transients were severely depressed in hearts with PTA and difficult to measure above background noise unless signal averaged or treated with isoproterenol (ISO). We confirmed that the reduced Ca2+ transients were due, at least partly, to a reduction in L-type Ca2+ current. In addition we found that although ISO could raise the L-type current in hearts with PTA to the level found in normal hearts in the absence of ISO, it could not fully restore the Ca2+ transient. Furthermore, caffeine-stimulated Ca2+ transients were diminished in size and the time-to-peak and the decaying phase were significantly slowed. Interestingly, these observations were not accompanied by a reduction in the number of Ca2+ release channels. These results indicated an impairment of SR function in addition to the reduction in L-type Ca2+ current. These results strongly support our hypothesis that the poor viability of embryos with PTA is due to impaired cardiac excitation-contraction coupling.
Creazzo
T L
TL
Institute of Molecular Medicine and Genetics, Development Biology Program, Medical College of Georgia, Augusta 30912-2640, USA.
Brotto
M A
MA
Burch
J
J
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002642:Chick Embryo; D016257:Fura-2; D009200:Myocardial Contraction / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011869:Radioligand Assay; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D013268:Stimulation, Chemical; D014339:Truncus Arteriosus, Persistent / Q000503:physiopathology*
D015220:Calcium Channels; D002110:Caffeine; D016257:Fura-2