Roles of Na/Ca Exchanger and Sarcoplasmic Reticulum Ca Clock in SinoAtrial Node Pacemaking: Insights from Bifurcation Analysis of a Mathematical Model
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概要
- 論文の詳細を見る
To elucidate the roles of Na/Ca exchanger (NCX) and sarcoplasmic reticulum (SR) Ca clock in sinoatrial node (SAN) pacemaking, we theoretically investigated 1) stability and bifurcation of the isolated SR Ca clock, 2) influences of NCX on stability of intracellular Ca<SUP>2+</SUP> dynamics and robustness of pacemaking, and 3) how SR Ca clock and NCX contribute to pacemaker activity of the full system. Bifurcation analyses were performed for mathematical models of rabbit SAN cells; equilibrium points (EPs), periodic orbits, and their stability were determined as functions of parameters. Isolated SR Ca clock exhibited spontaneous intracellular Ca oscillations around unstable EPs. Incorporating NCX currents stabilized EPs of the Ca clock system via Hopf bifurcations, abolishing spontaneous Ca oscillations. In the full system, reducing SR Ca uptake shrank unstable EP regions for the maximum conductance of L-type Ca channel current (g<SUB>Ca,L</SUB>) and constant bias currents via shifting bifurcation points. With relatively low g<SUB>Ca,L</SUB>, eliminating SR Ca clock abolished pacemaker activity via Hopf bifurcations. These results suggest that 1) SR Ca clock can generate spontaneous Ca oscillations but NCX stabilizes EPs to inhibit Ca oscillations; and 2) SR Ca clock enhances SAN cell robustness against attenuation of the membrane clock and hyperpolarizing loads.
- 日本不整脈学会の論文
著者
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Kurata Yasutaka
Department Of Cardiovascular Medicine Faculty Of Medicine Tottori University
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Shibamoto Toshishige
Department Of Physiology Ii Kanazawa Medical University
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Hisatome Ichiro
Division of Regenerative Medicine and Therapeutics, Tottori University Graduate School of Medical Science
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Hisatome Ichiro
Division of Cardiovascular Medicine, Department of Internal Medicine, Tottori University Faculty of Medicine
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Shibamoto Toshishige
Department of Physiology, Kanazawa Medical University
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