%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 }