LabHEART: An interactive computer model of rabbit ventricular myocyte ion channels and Ca transport

José L. Puglisi, Donald M Bers

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

An 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 (Ito) and inward rectifying K currents (IK1), 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 (INaCa) in HF lowers the intracellular [Ca] threshold for a triggered AP from 800 to 540 nM. Similarly, the decrease in IK1 reduces the threshold to 600 nM. Changes in Ito have no effect. Combining enhanced Na/Ca exchange with reduced IK1 (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 INaCa and IK1. A free copy of this software can be obtained at http://www.meddean.luc.edu/lumen/Dept/Webs/physio/bers.html.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume281
Issue number6 50-6
StatePublished - 2001
Externally publishedYes

Keywords

  • Excitation-contraction coupling
  • Heart failure
  • Mathematical model
  • Na/Ca exchange

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'LabHEART: An interactive computer model of rabbit ventricular myocyte ion channels and Ca transport'. Together they form a unique fingerprint.

  • Cite this