A compartmentalized mathematical model of mouse atrial myocytes

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • Georgia State University
  • University of Wisconsin-Madison

Details

Original languageEnglish (US)
Pages (from-to)H485-H507
JournalAmerican journal of physiology. Heart and circulatory physiology
Volume318
Issue number3
StatusPublished - Mar 1 2020
Peer-reviewedYes

Abstract

Various experimental mouse models are extensively used to research human diseases, including atrial fibrillation, the most common cardiac rhythm disorder. Despite this, there are no comprehensive mathematical models that describe the complex behavior of the action potential and [Ca2+]i transients in mouse atrial myocytes. Here, we develop a novel compartmentalized mathematical model of mouse atrial myocytes that combines the action potential, [Ca2+]i dynamics, and β-adrenergic signaling cascade for a subpopulation of right atrial myocytes with developed transverse-axial tubule system. The model consists of three compartments related to β-adrenergic signaling (caveolae, extracaveolae, and cytosol) and employs local control of Ca2+ release. It also simulates ionic mechanisms of action potential generation and describes atrial-specific Ca2+ handling as well as frequency dependences of the action potential and [Ca2+]i transients. The model showed that the T-type Ca2+ current significantly affects the later stage of the action potential, with little effect on [Ca2+]i transients. The block of the small-conductance Ca2+-activated K+ current leads to a prolongation of the action potential at high intracellular Ca2+. Simulation results obtained from the atrial model cells were compared with those from ventricular myocytes. The developed model represents a useful tool to study complex electrical properties in the mouse atria and could be applied to enhance the understanding of atrial physiology and arrhythmogenesis.NEW & NOTEWORTHY A new compartmentalized mathematical model of mouse right atrial myocytes was developed. The model simulated action potential and Ca2+ dynamics at baseline and after stimulation of the β-adrenergic signaling system. Simulations showed that the T-type Ca2+ current markedly prolonged the later stage of atrial action potential repolarization, with a minor effect on [Ca2+]i transients. The small-conductance Ca2+-activated K+ current block resulted in prolongation of the action potential only at the relatively high intracellular Ca2+.

    Research areas

  • Ca2+ dynamics, T-type Ca2+ channels, atrial action potential, small-conductance Ca2+-activated K+ channels, transverse-axial tubular system, β1-adrenergic signaling, β2-adrenergic signaling

Citation formats

APA

Asfaw, T. N., Tyan, L., Glukhov, A. V., & Bondarenko, V. E. (2020). A compartmentalized mathematical model of mouse atrial myocytes. American journal of physiology. Heart and circulatory physiology, 318(3), H485-H507. https://doi.org/10.1152/ajpheart.00460.2019

Harvard

Asfaw, TN, Tyan, L, Glukhov, AV & Bondarenko, VE 2020, 'A compartmentalized mathematical model of mouse atrial myocytes', American journal of physiology. Heart and circulatory physiology, vol. 318, no. 3, pp. H485-H507. https://doi.org/10.1152/ajpheart.00460.2019