The amplification factor of dihydropyridine (DHP)/ryanodine receptors
was defined as the amount of Ca2+ released from the sarcoplasmic
reticulum (SR) relative to the influx of Ca2+ through L-type Ca2+
channels in rat ventricular myocytes. The amplification factor showed
steep voltage dependence at potentials negative to -10 mV but was
less dependent on voltage at potentials positive to this value. In
cells dialyzed with 0.2 mM cAMP in addition to 2 mM fura 2, the Ca2+-channel
agonist (-)-BAY K 8644 enhanced Ca2+-channel current (ICa), shifted
the activation curve by -10 mV, and significantly delayed its inactivation.
Surprisingly, BAY K 8644 reduced the amplification factor by 50\%
at all potentials, even though the caffeine-releasable Ca2+ stores
were mostly intact at holding potentials of -90 mV. In contrast,
brief elevation of extracellular Ca2+ activity from 2 to 10 mM enhanced
both ICa and intracellular Ca2+ transients in the absence or presence
of BAY K 8644 but had no significant effect on the amplification
factor. BAY K 8644 abolished the direct dependence of the rate of
inactivation of ICa on the release of Ca2+ from the SR. These findings
suggest that the gain of the Ca2+-induced Ca2+ release in cardiac
myocytes is regulated by the gating kinetics of cardiac L-type Ca2+
channels via local exchange of Ca2+ signals between DHP and ryanodine
receptors and that BAY K 8644 suppresses the amplification factor
through attenuation of the Ca2+-dependent inactivation of Ca2+ channels.
Institute for Cardiovascular Sciences and Department of Pharmacology,
Georgetown University Medical Center, Washington, District of Columbia
20007, USA.
%0 Journal Article
%1 Adac_1999_1178
%A Adachi-Akahane, S.
%A Cleemann, L.
%A Morad, M.
%D 1999
%J Am J Physiol
%K 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, 3-Pyridinecarboxylic Agonists, Animals; Calcium Calcium, Channel Channel, Channels, Concentration; Conductivity; Electric Extracellular Heart L-Type; Methyl Myocardium, Osmolar Rats; Receptor Release Reticulum, Ryanodine Sarcoplasmic Signaling, Space, Ventricles; acid, cytology/metabolism; drug effects/metabolism effects/physiology; effects; ester, metabolism; pharmacology; physiology;
%N 4 Pt 2
%P H1178--H1189
%T BAY K 8644 modifies Ca2+ cross signaling between DHP and ryanodine
receptors in rat ventricular myocytes.
%V 276
%X The amplification factor of dihydropyridine (DHP)/ryanodine receptors
was defined as the amount of Ca2+ released from the sarcoplasmic
reticulum (SR) relative to the influx of Ca2+ through L-type Ca2+
channels in rat ventricular myocytes. The amplification factor showed
steep voltage dependence at potentials negative to -10 mV but was
less dependent on voltage at potentials positive to this value. In
cells dialyzed with 0.2 mM cAMP in addition to 2 mM fura 2, the Ca2+-channel
agonist (-)-BAY K 8644 enhanced Ca2+-channel current (ICa), shifted
the activation curve by -10 mV, and significantly delayed its inactivation.
Surprisingly, BAY K 8644 reduced the amplification factor by 50\%
at all potentials, even though the caffeine-releasable Ca2+ stores
were mostly intact at holding potentials of -90 mV. In contrast,
brief elevation of extracellular Ca2+ activity from 2 to 10 mM enhanced
both ICa and intracellular Ca2+ transients in the absence or presence
of BAY K 8644 but had no significant effect on the amplification
factor. BAY K 8644 abolished the direct dependence of the rate of
inactivation of ICa on the release of Ca2+ from the SR. These findings
suggest that the gain of the Ca2+-induced Ca2+ release in cardiac
myocytes is regulated by the gating kinetics of cardiac L-type Ca2+
channels via local exchange of Ca2+ signals between DHP and ryanodine
receptors and that BAY K 8644 suppresses the amplification factor
through attenuation of the Ca2+-dependent inactivation of Ca2+ channels.
@article{Adac_1999_1178,
abstract = {The amplification factor of dihydropyridine (DHP)/ryanodine receptors
was defined as the amount of Ca2+ released from the sarcoplasmic
reticulum (SR) relative to the influx of Ca2+ through L-type Ca2+
channels in rat ventricular myocytes. The amplification factor showed
steep voltage dependence at potentials negative to -10 mV but was
less dependent on voltage at potentials positive to this value. In
cells dialyzed with 0.2 mM cAMP in addition to 2 mM fura 2, the Ca2+-channel
agonist (-)-BAY K 8644 enhanced Ca2+-channel current (ICa), shifted
the activation curve by -10 mV, and significantly delayed its inactivation.
Surprisingly, BAY K 8644 reduced the amplification factor by 50\%
at all potentials, even though the caffeine-releasable Ca2+ stores
were mostly intact at holding potentials of -90 mV. In contrast,
brief elevation of extracellular Ca2+ activity from 2 to 10 mM enhanced
both ICa and intracellular Ca2+ transients in the absence or presence
of BAY K 8644 but had no significant effect on the amplification
factor. BAY K 8644 abolished the direct dependence of the rate of
inactivation of ICa on the release of Ca2+ from the SR. These findings
suggest that the gain of the Ca2+-induced Ca2+ release in cardiac
myocytes is regulated by the gating kinetics of cardiac L-type Ca2+
channels via local exchange of Ca2+ signals between DHP and ryanodine
receptors and that BAY K 8644 suppresses the amplification factor
through attenuation of the Ca2+-dependent inactivation of Ca2+ channels.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Adachi-Akahane, S. and Cleemann, L. and Morad, M.},
biburl = {https://www.bibsonomy.org/bibtex/25d19786f54af254c7498bd48651a1b7f/hake},
description = {The whole bibliography file I use.},
file = {Adac_1999_1178.pdf:Adac_1999_1178.pdf:PDF},
institution = {Institute for Cardiovascular Sciences and Department of Pharmacology,
Georgetown University Medical Center, Washington, District of Columbia
20007, USA.},
interhash = {27d6e3ee006b3cc18aeacc6bb7cb08f5},
intrahash = {5d19786f54af254c7498bd48651a1b7f},
journal = {Am J Physiol},
keywords = {1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, 3-Pyridinecarboxylic Agonists, Animals; Calcium Calcium, Channel Channel, Channels, Concentration; Conductivity; Electric Extracellular Heart L-Type; Methyl Myocardium, Osmolar Rats; Receptor Release Reticulum, Ryanodine Sarcoplasmic Signaling, Space, Ventricles; acid, cytology/metabolism; drug effects/metabolism effects/physiology; effects; ester, metabolism; pharmacology; physiology;},
month = Apr,
number = {4 Pt 2},
pages = {H1178--H1189},
pdf = {Adac_1999_1178.pdf},
pmid = {10199841},
timestamp = {2009-06-03T11:20:58.000+0200},
title = {BAY K 8644 modifies Ca2+ cross signaling between DHP and ryanodine
receptors in rat ventricular myocytes.},
volume = 276,
year = 1999
}