Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Oct 25;18(1):104.
doi: 10.1186/s12938-019-0723-5.

Stretch-activated current in human atrial myocytes and Na+ current and mechano-gated channels' current in myofibroblasts alter myocyte mechanical behavior: a computational study

Heqing Zhan  1 , Jingtao Zhang  2 , Anquan Jiao  3 , Qin Wang  3
Affiliations

Stretch-activated current in human atrial myocytes and Na+ current and mechano-gated channels' current in myofibroblasts alter myocyte mechanical behavior: a computational study

Heqing Zhan et al. Biomed Eng Online. .

Abstract

Background: The activation of stretch-activated channels (SACs) in cardiac myocytes, which changes the phases of action potential repolarization, is proven to be highly efficient for the conversion of atrial fibrillation. The expression of Na+ current in myofibroblasts (Mfbs) regenerates myocytes' action potentials, suggesting that Mfbs play an active role in triggering cardiac rhythm disturbances. Moreover, the excitation of mechano-gated channels (MGCs) in Mfbs depolarizes their membrane potential and contributes to the increased risk of post-infarct arrhythmia. Although these electrophysiological mechanisms have been largely known, the roles of these currents in cardiac mechanics are still debated. In this study, we aimed to investigate the mechanical influence of these currents via mathematical modeling. A novel mathematical model was developed by integrating models of human atrial myocyte (including the stretch-activated current, Ca2+-force relation, and mechanical behavior of a single segment) and Mfb (including our formulation of Na+ current and mechano-gated channels' current). The effects of the changes in basic cycle length, number of coupled Mfbs and intercellular coupling conductance on myocyte mechanical properties were compared.

Results: Our results indicated that these three currents significantly regulated myocyte mechanical parameters. In isosarcometric contraction, these currents increased segment force by 13.8-36.6% and dropped element length by 12.1-31.5%. In isotonic contraction, there are 2.7-5.9% growth and 0.9-24% reduction. Effects of these currents on the extremum of myocyte mechanical parameters become more significant with the increase of basic cycle length, number of coupled Mfbs and intercellular coupling conductance.

Conclusions: The results demonstrated that stretch-activated current in myocytes and Na+ current and mechano-gated channels' current in Mfbs significantly influenced myocyte mechanical behavior and should be considered in future cardiac mechanical mathematical modeling.

Keywords: Mathematical modeling; Mechano-gated channels (MGCs); Myocyte mechanics; Myofibroblast–myocyte (Mfb–M) coupling; Stretch-activated channels (SACs); Voltage-gated sodium channels (VGSCs).

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing of interests.

Figures

Fig. 1
Fig. 1
Effects of ISAC, INa_Mfb, and IMGC_Mfb on atrial myocyte a AP, b [Ca2+]i, and c Fnorm in five groups. BCL = 1 s, 2 Mfbs, Ggap = 3 nS
Fig. 2
Fig. 2
Effects of ISAC, INa_Mfb, and IMGC_Mfb on atrial myocyte segment mechanical parameters in isosarcometric contraction in five groups. BCL = 1 s, 2 Mfbs, Ggap = 3 nS
Fig. 3
Fig. 3
Effects of ISAC, INa_Mfb, and IMGC_Mfb on atrial myocyte segment mechanical parameters in isotonic contraction in five groups. BCL = 1 s, 2 Mfbs, Ggap = 3 nS
Fig. 4
Fig. 4
Effects of ISAC, INa_Mfb, and IMGC_Mfb on the extremum of FSE, Fsegment, lCE, and lSE as functions of BCL, Mfb–M ratio, and Ggap in isosarcometric contraction in five groups, a–d BCL = 0.1–2 s, Mfb:M = 2, Ggap = 3 nS, e–h BCL = 1 s, Mfb:M = 1–8, Ggap = 3 nS, and i–l BCL = 1 s, Mfb:M = 2, Ggap = 0.5–8 nS
Fig. 5
Fig. 5
Effects of ISAC, INa_Mfb, and IMGC_Mfb on the extremum of FSE, FPE, lCE, lSE, and lPE as functions of BCL, Mfb–M ratio, and Ggap in isosarcometric contraction in five groups. a–e BCL = 0.1–2 s, Mfb:M = 2, Ggap = 3 nS, f–j BCL = 1 s, Mfb:M = 1–8, Ggap = 3 nS, and k–o BCL = 1 s, Mfb:M = 2, Ggap = 0.5–8 nS
Fig. 6
Fig. 6
Three-element scheme to model mechanical behavior of a single segment
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Trayanova NA, Boyle PM. Advances in modeling ventricular arrhythmias: from mechanisms to the clinic. Wiley Interdiscipl Rev Syst Biol Med. 2014;6(2):209–224. doi: 10.1002/wsbm.1256. - DOI - PMC - PubMed
    1. Yang JH, Saucerman JJ. Computational models reduce complexity and accelerate insight into cardiac signaling networks. Circ Res. 2011;108(1):85–97. doi: 10.1161/CIRCRESAHA.110.223602. - DOI - PMC - PubMed
    1. Zaniboni M. Short-term action potential memory and electrical restitution: a cellular computational study on the stability of cardiac repolarization under dynamic pacing. PLoS ONE. 2018;13(3):e0193416. doi: 10.1371/journal.pone.0193416. - DOI - PMC - PubMed
    1. Sato D, Dixon RE, Santana LF, Navedo MF. A model for cooperative gating of L-type Ca2+ channels and its effects on cardiac alternans dynamics. PLoS Comput Biol. 2018;14(1):e1005906. doi: 10.1371/journal.pcbi.1005906. - DOI - PMC - PubMed
    1. Regazzoni F, Dede L, Quarteroni A. Active contraction of cardiac cells: a reduced model for sarcomere dynamics with cooperative interactions. Biomech Model Mechanobiol. 2018;17(6):1663–1686. doi: 10.1007/s10237-018-1049-0. - DOI - PubMed

LinkOut - more resources

  NODES
twitter 2