Modern perspectives on numerical modeling of cardiac pacemaker cell

Victor A. Maltsev, Yael Yaniv, Anna V. Maltsev, Michael D. Stern, Edward G. Lakatta

Research output: Contribution to journalReview articlepeer-review

Abstract

Cardiac pacemaking is a complex phenomenon that is still not completely understood. Together with experimental studies, numerical modeling has been traditionally used to acquire mechanistic insights in this research area. This review summarizes the present state of numerical modeling of the cardiac pacemaker, including approaches to resolve present paradoxes and controversies. Specifically we discuss the requirement for realistic modeling to consider symmetrical importance of both intracellular and cell membrane processes (within a recent "coupled-clock" theory). Promising future developments of the complex pacemaker system models include the introduction of local calcium control, mitochondria function, and biochemical regulation of protein phosphorylation and cAMP production. Modern numerical and theoretical methods such as multiparameter sensitivity analyses within extended populations of models and bifurcation analyses are also important for the definition of the most realistic parameters that describe a robust, yet simultaneously flexible operation of the coupled-clock pacemaker cell system. The systems approach to exploring cardiac pacemaker function will guide development of new therapies such as biological pacemakers for treating insufficient cardiac pacemaker function that becomes especially prevalent with advancing age.

Original languageEnglish (US)
Pages (from-to)6-38
Number of pages33
JournalJournal of Pharmacological Sciences
Volume125
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Calcium
  • Cardiac pacemaker
  • Ion channel
  • Numerical modeling
  • Sinoatrial node cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Modern perspectives on numerical modeling of cardiac pacemaker cell'. Together they form a unique fingerprint.

Cite this