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 language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Cell Physiology |
| Volume | 281 |
| Issue number | 6 50-6 |
| State | Published - 2001 |
| Externally published | Yes |
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Keywords
- Excitation-contraction coupling
- Heart failure
- Mathematical model
- Na/Ca exchange
ASJC Scopus subject areas
- Clinical Biochemistry
- Cell Biology
- Physiology
- Physiology (medical)
Cite this
LabHEART : An interactive computer model of rabbit ventricular myocyte ion channels and Ca transport. / Puglisi, José L.; Bers, Donald M.
In: American Journal of Physiology - Cell Physiology, Vol. 281, No. 6 50-6, 2001.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - LabHEART
T2 - An interactive computer model of rabbit ventricular myocyte ion channels and Ca transport
AU - Puglisi, José L.
AU - Bers, Donald M
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Excitation-contraction coupling
KW - Heart failure
KW - Mathematical model
KW - Na/Ca exchange
UR - http://www.scopus.com/inward/record.url?scp=0035658721&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035658721&partnerID=8YFLogxK
M3 - Article
C2 - 11698264
AN - SCOPUS:0035658721
VL - 281
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 6 50-6
ER -