%0 Journal Article %1 Tans_2005_85 %A Tanskanen, Antti J %A Greenstein, Joseph L %A O'Rourke, Brian %A Winslow, Raimond L %D 2005 %J Biophys. J. %K 15501946 AMP-Dependent Acid Action Adaptor Adrenergic, Algorithms, Amino Animals, Biological, Biophysics, Calcium Calcium, Cardiac, Cardiovascular, Cells, Chains, Channels, Complexes, Computer Conduction Cyclic Dependent Dogs, Electrophysiology, Expression Extramural, Factors, Gene Gov't, Guinea Heart Humans, Interaction Ions, Isoproterenol, Kinase, Kinases, L-Type, Long Mapping, Markov Membrane Models, Multiprotein Muscle Myocardium, Myocytes, N.I.H., Neurons, Non-U.S. P.H.S., Phosphatase, Phosphoprotein Phosphorylation, Pigs, Post-Translational, Potassium Potentials, Processes, Processing, Profiling, Protein Proteins, Proteome, Proteomics, QT Receptors, Regulation, Relationship, Research Ryanodine, Signal Simulation, Stochastic Structure-Activity Substitution, Support, Syndrome, System, Time Transducing, Transduction, U.S. Voltage-Gated, beta-1, {C}a$^{2+}$-Calmodulin %N 1 %P 85--95 %R 10.1529/biophysj.104.051508 %T The role of stochastic and modal gating of cardiac L-type Ca$^2+$ channels on early after-depolarizations. %U http://dx.doi.org/10.1529/biophysj.104.051508 %V 88 %X Certain signaling events that promote L-type Ca$^2+$ channel (LCC) phosphorylation, such as beta-adrenergic stimulation or an increased expression of Ca$^2+$/calmodulin-dependent protein kinase II, promote mode 2 gating of LCCs. Experimental data suggest the hypothesis that these events increase the likelihood of early after-depolarizations (EADs). We test this hypothesis using an ionic model of the canine ventricular myocyte incorporating stochastic gating of LCCs and ryanodine-sensitive calcium release channels. The model is extended to describe myocyte responses to the beta-adrenergic agonist isoproterenol. Results demonstrate that in the presence of isoproterenol the random opening of a small number of LCCs gating in mode 2 during the plateau phase of the action potential (AP) can trigger EADs. EADs occur randomly, where the likelihood of these events increases as a function of the fraction of LCCs gating in mode 2. Fluctuations of the L-type Ca$^2+$ current during the AP plateau lead to variability in AP duration. Consequently, prolonged APs are occasionally observed and exhibit an increased likelihood of EAD formation. These results suggest a novel stochastic mechanism, whereby phosphorylation-induced changes in LCC gating properties contribute to EAD generation.

@article{Tans_2005_85, abstract = {Certain signaling events that promote L-type {C}a$^{2+}$ channel (LCC) phosphorylation, such as beta-adrenergic stimulation or an increased expression of {C}a$^{2+}$/calmodulin-dependent protein kinase II, promote mode 2 gating of LCCs. Experimental data suggest the hypothesis that these events increase the likelihood of early after-depolarizations (EADs). We test this hypothesis using an ionic model of the canine ventricular myocyte incorporating stochastic gating of LCCs and ryanodine-sensitive calcium release channels. The model is extended to describe myocyte responses to the beta-adrenergic agonist isoproterenol. Results demonstrate that in the presence of isoproterenol the random opening of a small number of LCCs gating in mode 2 during the plateau phase of the action potential (AP) can trigger EADs. EADs occur randomly, where the likelihood of these events increases as a function of the fraction of LCCs gating in mode 2. Fluctuations of the L-type {C}a$^{2+}$ current during the AP plateau lead to variability in AP duration. Consequently, prolonged APs are occasionally observed and exhibit an increased likelihood of EAD formation. These results suggest a novel stochastic mechanism, whereby phosphorylation-induced changes in LCC gating properties contribute to EAD generation.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Tanskanen, Antti J and Greenstein, Joseph L and O'Rourke, Brian and Winslow, Raimond L}, biburl = {https://www.bibsonomy.org/bibtex/2ed39b0d194f591105a72acb10642fa6d/hake}, description = {The whole bibliography file I use.}, doi = {10.1529/biophysj.104.051508}, file = {Tans_2005_85.pdf:Tans_2005_85.pdf:PDF}, interhash = {5d193777bb1af552e074c892c486ca6c}, intrahash = {ed39b0d194f591105a72acb10642fa6d}, journal = {Biophys. J.}, keywords = {15501946 AMP-Dependent Acid Action Adaptor Adrenergic, Algorithms, Amino Animals, Biological, Biophysics, Calcium Calcium, Cardiac, Cardiovascular, Cells, Chains, Channels, Complexes, Computer Conduction Cyclic Dependent Dogs, Electrophysiology, Expression Extramural, Factors, Gene Gov't, Guinea Heart Humans, Interaction Ions, Isoproterenol, Kinase, Kinases, L-Type, Long Mapping, Markov Membrane Models, Multiprotein Muscle Myocardium, Myocytes, N.I.H., Neurons, Non-U.S. P.H.S., Phosphatase, Phosphoprotein Phosphorylation, Pigs, Post-Translational, Potassium Potentials, Processes, Processing, Profiling, Protein Proteins, Proteome, Proteomics, QT Receptors, Regulation, Relationship, Research Ryanodine, Signal Simulation, Stochastic Structure-Activity Substitution, Support, Syndrome, System, Time Transducing, Transduction, U.S. Voltage-Gated, beta-1, {C}a$^{2+}$-Calmodulin}, month = Jan, number = 1, pages = {85--95}, pii = {biophysj.104.051508}, pmid = {15501946}, timestamp = {2009-06-03T11:21:34.000+0200}, title = {The role of stochastic and modal gating of cardiac L-type {C}a$^{2+}$ channels on early after-depolarizations.}, url = {http://dx.doi.org/10.1529/biophysj.104.051508}, volume = 88, year = 2005 }