Abstract

OF WORK Software development on the full 3D model is proceding. The 2D grid model has been revised to include detailed balancing of whole-cell calcium balance. This model has been entirely recoded in compiled Java and spun out to run concurrently on all 48 processors of our local cluster with >70% efficiency. This has made it possible to explore parameters and identify several different new regimes of propagation relevant to the pacemaking function of SR calcium release in sin0-atrial node cells. Extensive simulations have been performed as a function of critical parameters regulating heart rate. The model successfully expalins the various regimes of localized and global calcium release and the transition among these regimes as a function of release current. These results are consistent with a new model of how heart rate is regulated by the autonomic nervous system. A publication is presently being reviewed by journal.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000844-14
Application #
8148327
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2010
Total Cost
$369,974
Indirect Cost

  Institution

Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Kim, Mary S; Maltsev, Alexander V; Monfredi, Oliver et al. (2018) Heterogeneity of calcium clock functions in dormant, dysrhythmically and rhythmically firing single pacemaker cells isolated from SA node. Cell Calcium 74:168-179
Monfredi, Oliver; Tsutsui, Kenta; Ziman, Bruce et al. (2018) Electrophysiological heterogeneity of pacemaker cells in the rabbit intercaval region, including the SA node: insights from recording multiple ion currents in each cell. Am J Physiol Heart Circ Physiol 314:H403-H414
Tsutsui, Kenta; Monfredi, Oliver J; Sirenko-Tagirova, Syevda G et al. (2018) A coupled-clock system drives the automaticity of human sinoatrial nodal pacemaker cells. Sci Signal 11:
Maltsev, Anna V; Maltsev, Victor A; Stern, Michael D (2017) Clusters of calcium release channels harness the Ising phase transition to confine their elementary intracellular signals. Proc Natl Acad Sci U S A 114:7525-7530
Maltsev, Alexander V; Parsons, Sean P; Kim, Mary S et al. (2017) Computer algorithms for automated detection and analysis of local Ca2+ releases in spontaneously beating cardiac pacemaker cells. PLoS One 12:e0179419
Maltsev, Alexander V; Maltsev, Victor A; Stern, Michael D (2017) Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release channels. PLoS Comput Biol 13:e1005675
Alexander-Shani, Rivka; Mreisat, Ahmad; Smeir, Elia et al. (2017) Long-term HIF-1? transcriptional activation is essential for heat-acclimation-mediated cross tolerance: mitochondrial target genes. Am J Physiol Regul Integr Comp Physiol 312:R753-R762
Stern, Michael D; Maltseva, Larissa A; Juhaszova, Magdalena et al. (2014) Hierarchical clustering of ryanodine receptors enables emergence of a calcium clock in sinoatrial node cells. J Gen Physiol 143:577-604
Maltsev, Victor A; Yaniv, Yael; Maltsev, Anna V et al. (2014) Modern perspectives on numerical modeling of cardiac pacemaker cell. J Pharmacol Sci 125:6-38
Stern, Michael D; Ríos, Eduardo; Maltsev, Victor A (2013) Life and death of a cardiac calcium spark. J Gen Physiol 142:257-74

Showing the most recent 10 out of 22 publications