Modeling the actions of beta-adrenergic signaling on excitation--contraction coupling processes. Export

@article{citeulike:690962, abstract = {Activation of the beta-adrenergic (beta-AR) signaling pathway enhances cardiac function through protein kinase A (PKA)-mediated phosphorylation of target proteins involved in the process of excitation-contraction (EC) coupling. Experimental studies of the effects of beta-AR stimulation on EC coupling have yielded complex results, including increased, decreased, or unchanged EC coupling gain. In this study, we extend a previously developed model of the canine ventricular myocyte describing local control of sarcoplasmic reticulum (SR) calcium (Ca(2+)) release to include the effects of beta-AR stimulation. Incorporation of phosphorylation-dependent effects on model membrane currents and Ca(2+)-cycling proteins yields changes of action potential (AP) and Ca(2+) transients in agreement with those measured experimentally in response to the nonspecific beta-AR agonist isoproterenol (ISO). The model reproduces experimentally observed alterations in EC coupling gain in response to beta-AR agonists and predicts the specific roles of L-type Ca(2+) channel (LCC) and SR Ca(2+) release channel phosphorylation in altering the amplitude and shape of the EC coupling gain function. The model also indicates that factors that promote mode 2 gating of LCCs, such as beta-AR stimulation or activation of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), may increase the probability of occurrence of early after-depolarizations (EADs), due to the random, long-duration opening of LCC gating in mode 2.}, address = {Center for Cardiovascular Bioinformatics and Modeling, The Johns Hopkins University School of Medicine, and Whiting School of Engineering, Baltimore, MD 21218, USA.}, author = {Greenstein, J. L. and Tanskanen, A. J. and Winslow, R. L.}, citeulike-article-id = {690962}, citeulike-linkout-0 = {http://dx.doi.org/10.1196/annals.1302.002}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15201146}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15201146}, doi = {10.1196/annals.1302.002}, issn = {0077-8923}, journal = {Ann N Y Acad Sci}, keywords = {beta, simualtion}, month = {May}, pages = {16--27}, posted-at = {2006-06-09 11:52:58}, priority = {5}, title = {Modeling the actions of beta-adrenergic signaling on excitation--contraction coupling processes.}, url = {http://dx.doi.org/10.1196/annals.1302.002}, volume = {1015}, year = {2004} }

TY - JOUR ID - citeulike:690962 L3 - citeulike-article-id:690962 N2 - Activation of the beta-adrenergic (beta-AR) signaling pathway enhances cardiac function through protein kinase A (PKA)-mediated phosphorylation of target proteins involved in the process of excitation-contraction (EC) coupling. Experimental studies of the effects of beta-AR stimulation on EC coupling have yielded complex results, including increased, decreased, or unchanged EC coupling gain. In this study, we extend a previously developed model of the canine ventricular myocyte describing local control of sarcoplasmic reticulum (SR) calcium (Ca(2+)) release to include the effects of beta-AR stimulation. Incorporation of phosphorylation-dependent effects on model membrane currents and Ca(2+)-cycling proteins yields changes of action potential (AP) and Ca(2+) transients in agreement with those measured experimentally in response to the nonspecific beta-AR agonist isoproterenol (ISO). The model reproduces experimentally observed alterations in EC coupling gain in response to beta-AR agonists and predicts the specific roles of L-type Ca(2+) channel (LCC) and SR Ca(2+) release channel phosphorylation in altering the amplitude and shape of the EC coupling gain function. The model also indicates that factors that promote mode 2 gating of LCCs, such as beta-AR stimulation or activation of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), may increase the probability of occurrence of early after-depolarizations (EADs), due to the random, long-duration opening of LCC gating in mode 2. JF - Ann N Y Acad Sci SN - 0077-8923 AD - Center for Cardiovascular Bioinformatics and Modeling, The Johns Hopkins University School of Medicine, and Whiting School of Engineering, Baltimore, MD 21218, USA. EP - 27 TI - Modeling the actions of beta-adrenergic signaling on excitation--contraction coupling processes. VL - 1015 SP - 16 KW - beta KW - simualtion AU - Greenstein, JL AU - Tanskanen, AJ AU - Winslow, RL PY - 2004/05// UR - http://dx.doi.org/10.1196/annals.1302.002 ER -