Ionic mechanisms for electrical heterogeneity between rabbit Purkinje fiber and ventricular cells.
The intrinsic heterogeneity of electrical action potential (AP) properties between Purkinje fibers (PFs) and the ventricular wall, as well as within the wall, plays an important role in ensuring successful excitation of the ventricles. It can also be proarrhythmic due to nonuniform repolarization across the Purkinje-ventricular junction. However, the ionic mechanisms that underlie the marked AP differences between PFs and ventricular cells are not fully characterized. We studied such mechanisms by developing a new family of biophysically detailed AP models for rabbit PF cells and three transmural ventricular cell types. The models were based on and validated against experimental data recorded from rabbit at ionic channel, single cell, and tissue levels. They were then used to determine the functional roles of each individual ionic channel current in modulating the AP heterogeneity at the rabbit Purkinje-ventricular junction, and to identify specific currents responsible for the differential response of PFs and ventricular cells to pharmacological interventions.
Aslanidi
Oleg V
OV
Biological Physics Group, School of Physics and Astronomy, University of Manchester, Manchester, United Kingdom.
Sleiman
Rakan N
RN
Boyett
Mark R
MR
Hancox
Jules C
JC
Zhang
Henggui
H
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003198:Computer Simulation; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008955:Models, Cardiovascular; D008959:Models, Neurological; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D011690:Purkinje Fibers / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D013997:Time Factors; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology*
D007473:Ion Channels; D012964:Sodium; D011188:Potassium; D002118:Calcium