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LabHEART: an interactive computer model of rabbit ventricular myocyte ion channels and Ca transportAn interactive computer program, LabHEART, was developed to simulate the action potential (AP), ionic currents, and Ca handling mechanisms in a rabbit ventricular myocyte. User-oriented, its design allows switching between voltage and current clamp and easy on-line manipulation of key parameters to change the original formulation. The model reproduces normal rabbit ventricular myocyte currents, Ca transients, and APs. We also changed parameters to simulate data from heart failure (HF) myocytes, including reduced transient outward (I(to)) and inward rectifying K currents (I(K1)), enhanced Na/Ca exchange expression, and reduced sarcoplasmic reticulum Ca-ATPase function, but unaltered Ca current density. These changes caused reduced Ca transient amplitude and increased AP duration (especially at lower frequency) as observed experimentally. The model shows that the increased Na/Ca exchange current (I(NaCa)) in HF lowers the intracellular [Ca] threshold for a triggered AP from 800 to 540 nM. Similarly, the decrease in I(K1) reduces the threshold to 600 nM. Changes in I(to) have no effect. Combining enhanced Na/Ca exchange with reduced I(K1) (as in HF) lowers the threshold to trigger an AP to 380 nM. These changes reproduce experimental results in HF, where the contributions of different factors are not readily distinguishable. We conclude that the triggered APs that contribute to nonreentrant ventricular tachycardia in HF are due approximately equally (and nearly additively) to alterations in I(NaCa) and I(K1). A free copy of this software can be obtained at http://www.meddean.luc.edu/lumen/DeptWebs/physio/bers.html.
Document ID
20040088669
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Puglisi, J. L.
(University of Illinois at Chicago, Stritch School of Medicine Maywood, Illinois 60153, United States)
Bers, D. M.
Date Acquired
August 21, 2013
Publication Date
December 1, 2001
Publication Information
Publication: American journal of physiology. Cell physiology
Volume: 281
Issue: 6
ISSN: 0363-6143
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: HL-30077
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Cardiopulmonary
Non-NASA Center

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