Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Decker, KF; Heijman, J; Silva, JR; Hund, TJ; Rudy, Y.
Properties and ionic mechanisms of action potential adaptation, restitution, and accommodation in canine epicardium
AM J PHYSIOL-HEART C. 2009; 296(4): H1017-H1026.
Doi: 10.1152/ajpheart.01216.2008
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Heijman Jordi
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Decker KF, Heijman J, Silva JR, Hund TJ, Rudy Y. Properties and ionic mechanisms of action potential adaptation, restitution, and accommodation in canine epicardium. Am J Physiol Heart Circ Physiol 296: H1017-H1026, 2009. First published January 23, 2009; doi:10.1152/ajpheart.01216.2008.-Computational models of cardiac myocytes are important tools for understanding ionic mechanisms of arrhythmia. This work presents a new model of the canine epicardial myocyte that reproduces a wide range of experimentally observed rate-dependent behaviors in cardiac cell and tissue, including action potential (AP) duration (APD) adaptation, restitution, and accommodation. Model behavior depends on updated formulations for the 4-aminopyridine-sensitive transient outward current (I-to1), the slow component of the delayed rectifier K+ current (I-Ks), the L-type Ca2+ channel current (I-Ca,I-L), and the Na+-K+ pump current (I-NaK) fit to data from canine ventricular myocytes. We found that I-to1 plays a limited role in potentiating peak I-Ca,I-L and sarcoplasmic reticulum Ca2+ release for propagated APs but modulates the time course of APD restitution. IKs plays an important role in APD shortening at short diastolic intervals, despite a limited role in AP repolarization at longer cycle lengths. In addition, we found that I-Ca,I-L plays a critical role in APD accommodation and rate dependence of APD restitution. Ca2+ entry via I-Ca,I-L at fast rate drives increased Na+-Ca2+ exchanger Ca2+ extrusion and Na+ entry, which in turn increases Na+ extrusion via outward I-NaK. APD accommodation results from this increased outward I-NaK. Our simulation results provide valuable insight into the mechanistic basis of rate-dependent phenomena important for determining the heart's response to rapid and irregular pacing rates (e.g., arrhythmia). Accurate simulation of rate-dependent phenomena and increased understanding of their mechanistic basis will lead to more realistic multicellular simulations of arrhythmia and identification of molecular therapeutic targets.
- Find related publications in this database (Keywords)
- arrhythmia
- cardiac electrophysiology
- mathematical modeling
- ion channels