Although a considerable number of studies have characterized inactivation
and facilitation of macroscopic L-type Ca(2+) channel currents, the
single channel properties underlying these important regulatory processes
have only rarely been examined using Ca(2+) ions. We have compared
unitary L-type Ca(2+) channel currents recorded with a low concentration
of Ca(2+) ions with those recorded with Ba(2+) ions to elucidate
the ionic dependence of the mechanisms responsible for the prepulse-dependent
modulation of Ca(2+) channel gating kinetics. Conditioning prepulses
were applied across a wide range of voltages to examine their effects
on the subsequent Ca(2+) channel activity, recorded at a constant
test potential. All recordings were made in the absence of any Ca(2+)
channel agonists. Moderate-depolarizing prepulses resulted in a decrease
in the probability of opening of the Ca(2+) channels during subsequent
test voltage steps (inactivation), the extent of which was more dramatic
with Ca(2+) ions than Ba(2+) ions. Facilitation, or increase of the
average probability of opening with strong predepolarization, was
due to long-duration mode 2 openings with Ca(2+) ions and Ba(2+)
ions, despite a decrease in Ca(2+) channel availability (inactivation)
under these conditions. The degree of both prepulse-induced inactivation
and facilitation decreased with increasing Ba(2+) ion concentration.
The time constants (and their proportions) describing the distributions
of Ca(2+) channel open times (which reflect mode switching) were
also prepulse-, and ion-dependent. These results support the hypothesis
that both prior depolarization and the nature and concentration of
permeant ions modulate the gating properties of cardiac L-type Ca(2+)
channels.
Laboratory of Cardiovascular Science, Gerontology Research Center,
National Institute on Aging, National Institutes of Health, 5600
Nathan Shock Drive, Baltimore, MD 21224, USA. josephsoni@grc.nia.nih.gov
%0 Journal Article
%1 Jose_2002_2575
%A Josephson, Ira R
%A Guia, Antonio
%A Lakatta, Edward G
%A Stern, Michael D
%D 2002
%J Biophys J
%K Animals; Barium, Calcium Calcium, Cells, Channels, Cultured; Electrophysiology; Factors Ions; Kinetics; L-Type, Male; Myocardium, Rats, Rats; Sprague-Dawley; Time chemistry/metabolism; chemistry; cytology;
%N 5
%P 2575--2586
%T Modulation of the gating of unitary cardiac L-type Ca(2+) channels
by conditioning voltage and divalent ions.
%U http://www.biophysj.org/cgi/content/full/83/5/2575
%V 83
%X Although a considerable number of studies have characterized inactivation
and facilitation of macroscopic L-type Ca(2+) channel currents, the
single channel properties underlying these important regulatory processes
have only rarely been examined using Ca(2+) ions. We have compared
unitary L-type Ca(2+) channel currents recorded with a low concentration
of Ca(2+) ions with those recorded with Ba(2+) ions to elucidate
the ionic dependence of the mechanisms responsible for the prepulse-dependent
modulation of Ca(2+) channel gating kinetics. Conditioning prepulses
were applied across a wide range of voltages to examine their effects
on the subsequent Ca(2+) channel activity, recorded at a constant
test potential. All recordings were made in the absence of any Ca(2+)
channel agonists. Moderate-depolarizing prepulses resulted in a decrease
in the probability of opening of the Ca(2+) channels during subsequent
test voltage steps (inactivation), the extent of which was more dramatic
with Ca(2+) ions than Ba(2+) ions. Facilitation, or increase of the
average probability of opening with strong predepolarization, was
due to long-duration mode 2 openings with Ca(2+) ions and Ba(2+)
ions, despite a decrease in Ca(2+) channel availability (inactivation)
under these conditions. The degree of both prepulse-induced inactivation
and facilitation decreased with increasing Ba(2+) ion concentration.
The time constants (and their proportions) describing the distributions
of Ca(2+) channel open times (which reflect mode switching) were
also prepulse-, and ion-dependent. These results support the hypothesis
that both prior depolarization and the nature and concentration of
permeant ions modulate the gating properties of cardiac L-type Ca(2+)
channels.
@article{Jose_2002_2575,
abstract = {Although a considerable number of studies have characterized inactivation
and facilitation of macroscopic L-type Ca(2+) channel currents, the
single channel properties underlying these important regulatory processes
have only rarely been examined using Ca(2+) ions. We have compared
unitary L-type Ca(2+) channel currents recorded with a low concentration
of Ca(2+) ions with those recorded with Ba(2+) ions to elucidate
the ionic dependence of the mechanisms responsible for the prepulse-dependent
modulation of Ca(2+) channel gating kinetics. Conditioning prepulses
were applied across a wide range of voltages to examine their effects
on the subsequent Ca(2+) channel activity, recorded at a constant
test potential. All recordings were made in the absence of any Ca(2+)
channel agonists. Moderate-depolarizing prepulses resulted in a decrease
in the probability of opening of the Ca(2+) channels during subsequent
test voltage steps (inactivation), the extent of which was more dramatic
with Ca(2+) ions than Ba(2+) ions. Facilitation, or increase of the
average probability of opening with strong predepolarization, was
due to long-duration mode 2 openings with Ca(2+) ions and Ba(2+)
ions, despite a decrease in Ca(2+) channel availability (inactivation)
under these conditions. The degree of both prepulse-induced inactivation
and facilitation decreased with increasing Ba(2+) ion concentration.
The time constants (and their proportions) describing the distributions
of Ca(2+) channel open times (which reflect mode switching) were
also prepulse-, and ion-dependent. These results support the hypothesis
that both prior depolarization and the nature and concentration of
permeant ions modulate the gating properties of cardiac L-type Ca(2+)
channels.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Josephson, Ira R and Guia, Antonio and Lakatta, Edward G and Stern, Michael D},
biburl = {https://www.bibsonomy.org/bibtex/22b916ea49785f9eb43c2a6b258666e0a/hake},
description = {The whole bibliography file I use.},
file = {Jose_2002_2575.pdf:Jose_2002_2575.pdf:PDF},
institution = {Laboratory of Cardiovascular Science, Gerontology Research Center,
National Institute on Aging, National Institutes of Health, 5600
Nathan Shock Drive, Baltimore, MD 21224, USA. josephsoni@grc.nia.nih.gov},
interhash = {62706b5b5e818d5f750bb4605097edac},
intrahash = {2b916ea49785f9eb43c2a6b258666e0a},
journal = {Biophys J},
keywords = {Animals; Barium, Calcium Calcium, Cells, Channels, Cultured; Electrophysiology; Factors Ions; Kinetics; L-Type, Male; Myocardium, Rats, Rats; Sprague-Dawley; Time chemistry/metabolism; chemistry; cytology;},
month = Nov,
number = 5,
pages = {2575--2586},
pdf = {Jose_2002_2575.pdf},
pmid = {12414691},
timestamp = {2009-06-03T11:21:17.000+0200},
title = {Modulation of the gating of unitary cardiac L-type Ca(2+) channels
by conditioning voltage and divalent ions.},
url = {http://www.biophysj.org/cgi/content/full/83/5/2575},
volume = 83,
year = 2002
}