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Characterization of cardiac L-type and T-type calcium channels during normal and defective chick heart development

Posted on:2001-08-24Degree:Ph.DType:Dissertation
University:Medical College of GeorgiaCandidate:Nichols, Carol AnnFull Text:PDF
GTID:1464390014459630Subject:Cellular biology
Abstract/Summary:
Ablation of the cardiac neural crest during early embryonic chick development produces persistent truncus arteriosus (PTA). Chick embryos with PTA have defective excitation-contraction coupling (ECC) as evidenced by reductions in ejection fractions, twitch force, Ca2+ transients, and L-type Ca2+ current (ICa,L) at embryonic day (ED)11 and ED15 (Creazzo, et al. 1998).;Previous work was done in pooled ventricles. The common truncus tends to override the right ventricle (RV) of PTA hearts, placing that ventricle under increased volume and pressure loads that might alter calcium channel function. Therefore, the RV and LV were examined separately in normal chick hearts and chick hearts with PTA at ED11 and ED15. ICa,L and T-type Ca+2 current (ICa,T) were measured. A significant reduction in ICa,L was seen in the LV of hearts with PTA compared to the LV of normal hearts at ED11, and in both the LV and RV of hearts with PTA at ED15. ICa,T was significantly smaller in both the LV and RV from hearts with PTA compared normal LV and RV at ED11 and in the RV of PTA hearts by ED15.;The decline in peak ICa,L is due, in part, to a reduction in the open channel probability (Po) of the L-type Ca+2 channel. At ED11 and ED15, Po is reduced in the RV and LV of hearts with PTA compared to respective ventricles from normal hearts. The reduced Po appears to be due to an absence of long openings of the channel.;Since a reduction in the number of Ca+2 channels would contribute to the reduction in ICa,L, (+)-[3H]PN200-110 was used for radiolabeling of dihydropyridine receptors (DHP-R). The was no difference in the number of DHP-R in ventricular myocytes from normal hearts or hearts with PTA at ED11 or ED15.;In summary, both ICa,L and ICa,T are reduced in both the RV and LV of hearts With PTA. The reduction of ICa,L is due to a decrease in Po, which is due to an absence of long channel openings. Although the number of DHP-R is not less in PTA hearts, channel function may be impaired.
Keywords/Search Tags:PTA, Channel, Chick, Normal, ED15, DHP-R, Ica, ED11
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