Molecular correlates of repolarization alternans in cardiac myocytes

Détails

ID Serval
serval:BIB_9D5BE4A446A9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Molecular correlates of repolarization alternans in cardiac myocytes
Périodique
Journal of Molecular and Cellular Cardiology
Auteur⸱e⸱s
Wan X., Laurita K.R., Pruvot E.J., Rosenbaum D.S.
ISSN
0022-2828 (Print)
Statut éditorial
Publié
Date de publication
09/2005
Volume
39
Numéro
3
Pages
419-28
Notes
Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. --- Old month value: Sep
Résumé
Arrhythmogenic action potential alternans (APD-ALT) is thought to arise from beat to beat alteration in cellular Ca(2+) cycling. Previously, we found that spatial heterogeneity in APD-ALT between ventricular myocytes is key to the mechanism linking APD-ALT to cardiac arrhythmogenesis. However, the cellular and molecular basis for APD-ALT is poorly understood. To test the hypothesis that spatial heterogeneities in expression and function of calcium cycling proteins underlies heterogeneities in APD-ALT, endocardial and epicardial myocytes were isolated from left ventricular free wall of 20 guinea pig hearts. APD-ALT and Ca(2+) transient alternans (Ca-ALT) were measured simultaneously as stimulus rate was increased progressively. Endocardial myocytes exhibited greater susceptibility to cellular alternans than epicardial myocytes as evidenced by a significantly lower pacing rate threshold for APD-ALT (113 +/ -9 bpm vs. 151 +/- 8 bpm, respectively, P < 0.05) and for Ca-ALT (110 +/- 8 bpm vs. 149 +/- 8 bpm, respectively, P < 0.05). APD-ALT never occurred without Ca-ALT, whereas Ca-ALT was readily induced in the absence of APD-ALT by repetitive constant action potential waveform, suggesting that Ca-ALT was not secondary to APD-ALT. Importantly, there were significant voltage-independent differences in Ca(2+) cycling between endocardial and epicardial myocytes as evidenced by weaker Ca(2+) release (32% lower Ca(2+) amplitude, and 16% longer rise time), and slower Ca(2+) reuptake (24% larger Ca(2+) decay time constant, and 9% longer Ca(2+) transient duration) in endocardial compared to epicardial myocytes. Taken together these data indicate that myocytes that are most susceptible to APD-ALT exhibit impaired Ca(2+) release and reuptake. Moreover, transmural differences in Ca(2+) cycling function was associated with significantly reduced endocardial expression of ryanodine release channel (by 22%) and SERCA2 (by 40%), suggesting a potential molecular basis for spatially heterogeneous APD-ALT. Moreover, transmural differences in expression and function of key SR Ca(2+) cycling proteins may underlie spatial heterogeneity of APD-ALT that has been closely linked to cardiac arrhythmogenesis.
Mots-clé
Action Potentials Animals Arrhythmia/*etiology Blotting, Western Calcium/*metabolism Calcium Channels, L-Type/analysis/metabolism Calcium-Binding Proteins/analysis/metabolism Calcium-Transporting ATPases/analysis/metabolism Cardiac Pacing, Artificial Endocardium/cytology Guinea Pigs Heart Conduction System/*physiopathology Heart Ventricles/cytology Myocytes, Cardiac/*physiology Patch-Clamp Techniques Pericardium/cytology Ryanodine Receptor Calcium Release Channel/analysis/metabolism Sarcoplasmic Reticulum Calcium-Transporting ATPases Sodium-Calcium Exchanger/analysis/metabolism
Pubmed
Web of science
Création de la notice
28/01/2008 10:04
Dernière modification de la notice
20/08/2019 15:03
Données d'usage