Excitation-contraction coupling and extracellular calcium transients
in rabbit atrium: reconstruction of basic cellular mechanisms.
D. Hilgemann, and D. Noble. Proc. R. Soc. Lond. B. Biol. Sci., 230 (1259):
163--205(March 1987)
Abstract
Interactions of electrogenic sodium-calcium exchange, calcium channel
and sarcoplasmic reticulum in the mammalian heart have been explored
by simulation of extracellular calcium transients measured with tetramethylmurexide
in rabbit atrium. The approach has been to use the simplest possible
formulations of these mechanisms, which together with a minimum number
of additional mechanisms allow reconstruction of action potentials,
intracellular calcium transients and extracellular calcium transients.
A 3:1 sodium-calcium exchange stoichiometry is assumed. Calcium-channel
inactivation is assumed to take place by a voltage-dependent mechanism,
which is accelerated by a rise in intracellular calcium; intracellular
calcium release becomes a major physiological regulator of calcium
influx via calcium channels. A calcium release mechanism is assumed,
which is both calcium- and voltage-sensitive, and which undergoes
prolonged inactivation. 200 microM cytosolic calcium buffer is assumed.
For most simulations only instantaneous potassium conductances are
simulated so as to study the other mechanisms independently of time-
and calcium-dependent outward current. Thus, the model reconstructs
extracellular calcium transients and typical action-potential configuration
changes during steady-state and non-steady-state stimulation from
the mechanisms directly involved in trans-sarcolemmal calcium movements.
The model predicts relatively small trans-sarcolemmal calcium movements
during regular stimulation (ca. 2 mumol kg-1 fresh mass per excitation);
calcium current is fully activated within 2 ms of excitation, inactivation
is substantially complete within 30 ms, and sodium-calcium exchange
significantly resists repolarization from approximately -30 mV. Net
calcium movements many times larger are possible during non-steady-state
stimulation. Long action potentials at premature excitations or after
inhibition of calcium release can be supported almost exclusively
by calcium current (net calcium influx 5-30 mumol kg-1 fresh mass);
action potentials during potentiated post-stimulatory contractions
can be supported almost exclusively by sodium-calcium exchange (net
calcium efflux 4-20 mumol kg-1 fresh mass). Large calcium movements
between the extracellular space and the sarcoplasmic reticulum can
take place through the cytosol with virtually no contractile activation.
The simulations provide integrated explanations of electrical activity,
contractile function and trans-sarcolemmal calcium movements, which
were outside the explanatory range of previous models.
%0 Journal Article
%1 Hilg_1987_163
%A Hilgemann, D. W.
%A Noble, D.
%D 1987
%J Proc. R. Soc. Lond. B. Biol. Sci.
%K 2884668 Animals, Atria, Atrial Calcium, Contraction, Function, Gov't, Heart Myocardial Non-U.S. Rabbits, Research Support,
%N 1259
%P 163--205
%T Excitation-contraction coupling and extracellular calcium transients
in rabbit atrium: reconstruction of basic cellular mechanisms.
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2884668&query_hl=39
%V 230
%X Interactions of electrogenic sodium-calcium exchange, calcium channel
and sarcoplasmic reticulum in the mammalian heart have been explored
by simulation of extracellular calcium transients measured with tetramethylmurexide
in rabbit atrium. The approach has been to use the simplest possible
formulations of these mechanisms, which together with a minimum number
of additional mechanisms allow reconstruction of action potentials,
intracellular calcium transients and extracellular calcium transients.
A 3:1 sodium-calcium exchange stoichiometry is assumed. Calcium-channel
inactivation is assumed to take place by a voltage-dependent mechanism,
which is accelerated by a rise in intracellular calcium; intracellular
calcium release becomes a major physiological regulator of calcium
influx via calcium channels. A calcium release mechanism is assumed,
which is both calcium- and voltage-sensitive, and which undergoes
prolonged inactivation. 200 microM cytosolic calcium buffer is assumed.
For most simulations only instantaneous potassium conductances are
simulated so as to study the other mechanisms independently of time-
and calcium-dependent outward current. Thus, the model reconstructs
extracellular calcium transients and typical action-potential configuration
changes during steady-state and non-steady-state stimulation from
the mechanisms directly involved in trans-sarcolemmal calcium movements.
The model predicts relatively small trans-sarcolemmal calcium movements
during regular stimulation (ca. 2 mumol kg-1 fresh mass per excitation);
calcium current is fully activated within 2 ms of excitation, inactivation
is substantially complete within 30 ms, and sodium-calcium exchange
significantly resists repolarization from approximately -30 mV. Net
calcium movements many times larger are possible during non-steady-state
stimulation. Long action potentials at premature excitations or after
inhibition of calcium release can be supported almost exclusively
by calcium current (net calcium influx 5-30 mumol kg-1 fresh mass);
action potentials during potentiated post-stimulatory contractions
can be supported almost exclusively by sodium-calcium exchange (net
calcium efflux 4-20 mumol kg-1 fresh mass). Large calcium movements
between the extracellular space and the sarcoplasmic reticulum can
take place through the cytosol with virtually no contractile activation.
The simulations provide integrated explanations of electrical activity,
contractile function and trans-sarcolemmal calcium movements, which
were outside the explanatory range of previous models.
@article{Hilg_1987_163,
abstract = {Interactions of electrogenic sodium-calcium exchange, calcium channel
and sarcoplasmic reticulum in the mammalian heart have been explored
by simulation of extracellular calcium transients measured with tetramethylmurexide
in rabbit atrium. The approach has been to use the simplest possible
formulations of these mechanisms, which together with a minimum number
of additional mechanisms allow reconstruction of action potentials,
intracellular calcium transients and extracellular calcium transients.
A 3:1 sodium-calcium exchange stoichiometry is assumed. Calcium-channel
inactivation is assumed to take place by a voltage-dependent mechanism,
which is accelerated by a rise in intracellular calcium; intracellular
calcium release becomes a major physiological regulator of calcium
influx via calcium channels. A calcium release mechanism is assumed,
which is both calcium- and voltage-sensitive, and which undergoes
prolonged inactivation. 200 microM cytosolic calcium buffer is assumed.
For most simulations only instantaneous potassium conductances are
simulated so as to study the other mechanisms independently of time-
and calcium-dependent outward current. Thus, the model reconstructs
extracellular calcium transients and typical action-potential configuration
changes during steady-state and non-steady-state stimulation from
the mechanisms directly involved in trans-sarcolemmal calcium movements.
The model predicts relatively small trans-sarcolemmal calcium movements
during regular stimulation (ca. 2 mumol kg-1 fresh mass per excitation);
calcium current is fully activated within 2 ms of excitation, inactivation
is substantially complete within 30 ms, and sodium-calcium exchange
significantly resists repolarization from approximately -30 mV. Net
calcium movements many times larger are possible during non-steady-state
stimulation. Long action potentials at premature excitations or after
inhibition of calcium release can be supported almost exclusively
by calcium current (net calcium influx 5-30 mumol kg-1 fresh mass);
action potentials during potentiated post-stimulatory contractions
can be supported almost exclusively by sodium-calcium exchange (net
calcium efflux 4-20 mumol kg-1 fresh mass). Large calcium movements
between the extracellular space and the sarcoplasmic reticulum can
take place through the cytosol with virtually no contractile activation.
The simulations provide integrated explanations of electrical activity,
contractile function and trans-sarcolemmal calcium movements, which
were outside the explanatory range of previous models.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Hilgemann, D. W. and Noble, D.},
biburl = {https://www.bibsonomy.org/bibtex/24c25127bc40dc3a91a1f1e529246d061/hake},
description = {The whole bibliography file I use.},
interhash = {502738ae8cb663994e27bde38331eb88},
intrahash = {4c25127bc40dc3a91a1f1e529246d061},
journal = {Proc. R. Soc. Lond. B. Biol. Sci.},
key = 78,
keywords = {2884668 Animals, Atria, Atrial Calcium, Contraction, Function, Gov't, Heart Myocardial Non-U.S. Rabbits, Research Support,},
month = Mar,
number = 1259,
pages = {163--205},
pmid = {2884668},
timestamp = {2009-06-03T11:21:14.000+0200},
title = {Excitation-contraction coupling and extracellular calcium transients
in rabbit atrium: reconstruction of basic cellular mechanisms.},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2884668&query_hl=39},
volume = 230,
year = 1987
}