Changes in cytosolic free Mg(2+) and adenosine nucleotide phosphates
affect cardiac excitability and contractility. To investigate how
modulation by Mg(2+), ATP, and ADP of K(ATP) and L-type Ca(2+) channels
influences excitation-contraction coupling, we incorporated equations
for intracellular ATP and MgADP regulation of the K(ATP) current
and MgATP regulation of the L-type Ca(2+) current in an ionic-metabolic
model of the canine ventricular myocyte. The new model: 1), quantitatively
reproduces a dose-response relationship for the effects of changes
in ATP on K(ATP) current, 2), simulates effects of ADP in modulating
ATP sensitivity of K(ATP) channel, 3), predicts activation of Ca(2+)
current during rapid increase in MgATP, and 4), demonstrates that
decreased ATP/ADP ratio with normal total Mg(2+) or increased free
Mg(2+) with normal ATP and ADP activate K(ATP) current, shorten action
potential, and alter ionic currents and intracellular Ca(2+) signals.
The model predictions are in agreement with experimental data measured
under normal and a variety of pathological conditions.
%0 Journal Article
%1 Mich_2005_2234
%A Michailova, Anushka
%A Saucerman, Jeffrey
%A Belik, Mary Ellen
%A McCulloch, Andrew D
%D 2005
%J Biophys J
%K Adenosine Calcium Cardiac, Cardiovascular; Cells, Channel Channels, Computer Contraction, Cultured; Diphosphate, Gating, Homeostasis, Ion L-Type, Magnesium, Models, Myocardial Myocytes, Potassium Signal Signaling, Simulation; Transduction, Triphosphate, metabolism; physiology physiology;
%N 3
%P 2234--2249
%R 10.1529/biophysj.104.046284
%T Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP,
ADP, and Mg2+.
%U http://dx.doi.org/10.1529/biophysj.104.046284
%V 88
%X Changes in cytosolic free Mg(2+) and adenosine nucleotide phosphates
affect cardiac excitability and contractility. To investigate how
modulation by Mg(2+), ATP, and ADP of K(ATP) and L-type Ca(2+) channels
influences excitation-contraction coupling, we incorporated equations
for intracellular ATP and MgADP regulation of the K(ATP) current
and MgATP regulation of the L-type Ca(2+) current in an ionic-metabolic
model of the canine ventricular myocyte. The new model: 1), quantitatively
reproduces a dose-response relationship for the effects of changes
in ATP on K(ATP) current, 2), simulates effects of ADP in modulating
ATP sensitivity of K(ATP) channel, 3), predicts activation of Ca(2+)
current during rapid increase in MgATP, and 4), demonstrates that
decreased ATP/ADP ratio with normal total Mg(2+) or increased free
Mg(2+) with normal ATP and ADP activate K(ATP) current, shorten action
potential, and alter ionic currents and intracellular Ca(2+) signals.
The model predictions are in agreement with experimental data measured
under normal and a variety of pathological conditions.
@article{Mich_2005_2234,
abstract = {Changes in cytosolic free Mg(2+) and adenosine nucleotide phosphates
affect cardiac excitability and contractility. To investigate how
modulation by Mg(2+), ATP, and ADP of K(ATP) and L-type Ca(2+) channels
influences excitation-contraction coupling, we incorporated equations
for intracellular ATP and MgADP regulation of the K(ATP) current
and MgATP regulation of the L-type Ca(2+) current in an ionic-metabolic
model of the canine ventricular myocyte. The new model: 1), quantitatively
reproduces a dose-response relationship for the effects of changes
in ATP on K(ATP) current, 2), simulates effects of ADP in modulating
ATP sensitivity of K(ATP) channel, 3), predicts activation of Ca(2+)
current during rapid increase in MgATP, and 4), demonstrates that
decreased ATP/ADP ratio with normal total Mg(2+) or increased free
Mg(2+) with normal ATP and ADP activate K(ATP) current, shorten action
potential, and alter ionic currents and intracellular Ca(2+) signals.
The model predictions are in agreement with experimental data measured
under normal and a variety of pathological conditions.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Michailova, Anushka and Saucerman, Jeffrey and Belik, Mary Ellen and McCulloch, Andrew D},
biburl = {https://www.bibsonomy.org/bibtex/224a06278d96258b34abbc100237ad97a/hake},
description = {The whole bibliography file I use.},
doi = {10.1529/biophysj.104.046284},
file = {Mich_2005_2234.pdf:Mich_2005_2234.pdf:PDF},
institution = {U CA, San Diego},
interhash = {88c190d38cc1768a3be25afc2ac0cb31},
intrahash = {24a06278d96258b34abbc100237ad97a},
journal = {Biophys J},
keywords = {Adenosine Calcium Cardiac, Cardiovascular; Cells, Channel Channels, Computer Contraction, Cultured; Diphosphate, Gating, Homeostasis, Ion L-Type, Magnesium, Models, Myocardial Myocytes, Potassium Signal Signaling, Simulation; Transduction, Triphosphate, metabolism; physiology physiology;},
month = Mar,
number = 3,
pages = {2234--2249},
pdf = {Mich_2005_2234.pdf},
pii = {biophysj.104.046284},
pmid = {15738467},
timestamp = {2009-06-03T11:21:23.000+0200},
title = {Modeling regulation of cardiac KATP and L-type Ca2+ currents by ATP,
ADP, and Mg2+.},
url = {http://dx.doi.org/10.1529/biophysj.104.046284},
volume = 88,
year = 2005
}