The relative contributions of voltage- and Ca$^2+$-dependent mechanisms
of inactivation to the decay of L-type Ca$^2+$ channel currents
(I(CaL)) is an old story to which recent results have given an unexpected
twist. In cardiac myocytes voltage-dependent inactivation (VDI) was
thought to be slow and Ca$^2+$-dependent inactivation (CDI) resulting
from Ca$^2+$ influx and Ca$^2+$-induced Ca$^2+$-release
(CICR) from the sarcoplasmic reticulum provided an automatic negative
feedback mechanism to limit Ca$^2+$ entry and the contribution
of I(CaL) to the cardiac action potential. Physiological modulation
of I(CaL) by Beta-adrenergic and muscarinic agonists then involved
essentially more or less of the same by enhancing or reducing Ca$^2+$
channel activity, Ca$^2+$ influx, sarcoplasmic reticulum load
and thus CDI. Recent results on the other hand place VDI at the centre
of the regulation of I(CaL). Under basal conditions it has been found
that depolarization increases the probability that an ion channel
will show rapid VDI. This is prevented by Beta-adrenergic stimulation.
Evidence also suggests that a channel which shows rapid VDI inactivates
before CDI can become effective. Therefore the contributions of VDI
and CDI to the decay of I(CaL) are determined by the turning on,
by depolarization, and the turning off, by phosphorylation, of the
mechanism of rapid VDI. The physiological implications of these ideas
are that under basal conditions the contribution of I(CaL) to the
action potential will be determined largely by voltage and by Ca$^2+$
following Beta-adrenergic stimulation.
%0 Journal Article
%1 Find_2004_275
%A Findlay, Ian
%D 2004
%J J. Physiol.
%K 80 AMP, Accident, Acids, Action Adrenergic Adult, Aged, Agents, Aggregation An, Animals, Anticoagulants, Aspirin, Atria, Atrial Attitude Benzoic Britain, Calcium Calcium, Cardiac, Cardiomyopathy, Cardiotonic Cell Cells, Cerebrovascular Channels, Chloride Chlorides, Comparative Conductance Conductivity, Consent, Cultured, Cyclic Cystic Cystic, Dilated, Diseases, Division, Dogs, Dose-Response Drug, Electric Electrophysiology, Epithelium, Feasibility Female, Fibrillation, Fibrosis Forskolin, Genistein, Glyburide, Gov't, Great Guinea Health, Heart Hospital, Hospitalization, Humans, Infarction, Informed Inhibitors, Ion Isoproterenol, Kidney, L-Type, Line, Male, Medical Membrane Middle Muscle Myocardial Myocardium, Myocytes, Nitrobenzoates, Non-U.S. Patch-Clamp Physician's Pigs, Platelet Potentials, Regulator, Relationship, Role, Staff, Stimulation, Studies, Study, Techniques, Transmembrane Transport, Ventricles, and beta-Agonists, beta-Antagonists, over, to
%N Pt 2
%P 275--283
%R 10.1113/jphysiol.2003.047902
%T Physiological modulation of inactivation in L-type Ca$^2+$ channels:
one switch.
%U http://dx.doi.org/10.1113/jphysiol.2003.047902
%V 554
%X The relative contributions of voltage- and Ca$^2+$-dependent mechanisms
of inactivation to the decay of L-type Ca$^2+$ channel currents
(I(CaL)) is an old story to which recent results have given an unexpected
twist. In cardiac myocytes voltage-dependent inactivation (VDI) was
thought to be slow and Ca$^2+$-dependent inactivation (CDI) resulting
from Ca$^2+$ influx and Ca$^2+$-induced Ca$^2+$-release
(CICR) from the sarcoplasmic reticulum provided an automatic negative
feedback mechanism to limit Ca$^2+$ entry and the contribution
of I(CaL) to the cardiac action potential. Physiological modulation
of I(CaL) by Beta-adrenergic and muscarinic agonists then involved
essentially more or less of the same by enhancing or reducing Ca$^2+$
channel activity, Ca$^2+$ influx, sarcoplasmic reticulum load
and thus CDI. Recent results on the other hand place VDI at the centre
of the regulation of I(CaL). Under basal conditions it has been found
that depolarization increases the probability that an ion channel
will show rapid VDI. This is prevented by Beta-adrenergic stimulation.
Evidence also suggests that a channel which shows rapid VDI inactivates
before CDI can become effective. Therefore the contributions of VDI
and CDI to the decay of I(CaL) are determined by the turning on,
by depolarization, and the turning off, by phosphorylation, of the
mechanism of rapid VDI. The physiological implications of these ideas
are that under basal conditions the contribution of I(CaL) to the
action potential will be determined largely by voltage and by Ca$^2+$
following Beta-adrenergic stimulation.
@article{Find_2004_275,
abstract = {The relative contributions of voltage- and {C}a$^{2+}$-dependent mechanisms
of inactivation to the decay of L-type {C}a$^{2+}$ channel currents
(I(CaL)) is an old story to which recent results have given an unexpected
twist. In cardiac myocytes voltage-dependent inactivation (VDI) was
thought to be slow and {C}a$^{2+}$-dependent inactivation (CDI) resulting
from {C}a$^{2+}$ influx and {C}a$^{2+}$-induced {C}a$^{2+}$-release
(CICR) from the sarcoplasmic reticulum provided an automatic negative
feedback mechanism to limit {C}a$^{2+}$ entry and the contribution
of I(CaL) to the cardiac action potential. Physiological modulation
of I(CaL) by Beta-adrenergic and muscarinic agonists then involved
essentially more or less of the same by enhancing or reducing {C}a$^{2+}$
channel activity, {C}a$^{2+}$ influx, sarcoplasmic reticulum load
and thus CDI. Recent results on the other hand place VDI at the centre
of the regulation of I(CaL). Under basal conditions it has been found
that depolarization increases the probability that an ion channel
will show rapid VDI. This is prevented by Beta-adrenergic stimulation.
Evidence also suggests that a channel which shows rapid VDI inactivates
before CDI can become effective. Therefore the contributions of {VDI}
and CDI to the decay of I(CaL) are determined by the turning on,
by depolarization, and the turning off, by phosphorylation, of the
mechanism of rapid VDI. The physiological implications of these ideas
are that under basal conditions the contribution of I(CaL) to the
action potential will be determined largely by voltage and by {C}a$^{2+}$
following Beta-adrenergic stimulation.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Findlay, Ian},
biburl = {https://www.bibsonomy.org/bibtex/2b4733774d733aa792a0605c406fbe30b/hake},
description = {The whole bibliography file I use.},
doi = {10.1113/jphysiol.2003.047902},
file = {Find_2004_275.pdf:Find_2004_275.pdf:PDF},
interhash = {aa400fbdc3e746f406e6a79b21465954},
intrahash = {b4733774d733aa792a0605c406fbe30b},
journal = {J. Physiol.},
key = 191,
keywords = {80 AMP, Accident, Acids, Action Adrenergic Adult, Aged, Agents, Aggregation An, Animals, Anticoagulants, Aspirin, Atria, Atrial Attitude Benzoic Britain, Calcium Calcium, Cardiac, Cardiomyopathy, Cardiotonic Cell Cells, Cerebrovascular Channels, Chloride Chlorides, Comparative Conductance Conductivity, Consent, Cultured, Cyclic Cystic Cystic, Dilated, Diseases, Division, Dogs, Dose-Response Drug, Electric Electrophysiology, Epithelium, Feasibility Female, Fibrillation, Fibrosis Forskolin, Genistein, Glyburide, Gov't, Great Guinea Health, Heart Hospital, Hospitalization, Humans, Infarction, Informed Inhibitors, Ion Isoproterenol, Kidney, L-Type, Line, Male, Medical Membrane Middle Muscle Myocardial Myocardium, Myocytes, Nitrobenzoates, Non-U.S. Patch-Clamp Physician's Pigs, Platelet Potentials, Regulator, Relationship, Role, Staff, Stimulation, Studies, Study, Techniques, Transmembrane Transport, Ventricles, and beta-Agonists, beta-Antagonists, over, to},
month = Jan,
number = {Pt 2},
pages = {275--283},
pii = {jphysiol.2003.047902},
pmid = {12824441},
timestamp = {2009-06-03T11:21:11.000+0200},
title = {Physiological modulation of inactivation in L-type {C}a$^{2+}$ channels:
one switch.},
url = {http://dx.doi.org/10.1113/jphysiol.2003.047902},
volume = 554,
year = 2004
}