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2016 Fiscal Year Final Research Report

Insights into pacemaker mechanisms for human stem cell-derived cardiomyocytes with application to biological pacemaker engineering

Research Project

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Project/Area Number 26460303
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General physiology
Research InstitutionKanazawa Medical University

Principal Investigator

KURATA Yasutaka  金沢医科大学, 医学部, 教授 (00267725)

Project Period (FY) 2014-04-01 – 2017-03-31
Keywordscardiac pacemaker / mathematical model / bifurcation analysis / computer simulation
Outline of Final Research Achievements

We have developed mathematical models for ES/iPS cell-derived cardiomyocytes as modified versions of the human ventricular and atrial myocyte models. By bifurcation analyses for the model cells, we have found that automaticity of sinoatrial node cell-like pacemaker cells is attributable to the destabilization of the equilibrium point (EP) via L-type Ca channel currents, whereas cessation of pacemaker activity of atrial or ventricular cell-like cardiomyocytes is due to the emergence of a stable EP via increase of inward-rectifier K channel currents. We further developed a multi-cellular model composed of pacemaker cells and atrial/ventricular cells, and examined functions of the pacemaker cell as a biological pacemaker. Incorporating pacemaker currents into the pacemaker cell altered functions of the biological pacemaker in the multicellular model. Incorporation of the sustained inward current was found to be most effective in the enhancement of biological pacemaker functions.

Free Research Field

システム生理学

URL: 

Published: 2018-03-22  

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