Bifurcation Analysis of Genetically Engineered Pacemaking in Mammalian Heart |
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Authors: | Wing Chiu Tong Arun V Holden |
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Institution: | (1) Computational Biology Laboratory, Institute of Membrane and Systems Biology, University of Leeds, Leeds, LS2 9JT, UK |
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Abstract: | Genetically engineered pacemaking in ventricular cells has been achieved by down-regulation of the time independent inward rectifying current (I
K1), or insertion of the hyperpolarisation-activated funny current (I
f). We analyse the membrane system (i.e. ionic concentrations clamped) of an epicardial Luo-Rudy dynamic cell model using continuation algorithms with the maximum conductance ( ) of I
K1 and I
f as bifurcation parameters. Pacemaker activity can be induced either via Hopf or homoclinic bifurcations. As
K1 is decreased by ≈74%, autorhythmicity emerged via a homoclinic bifurcation, i.e., the periodicity first appear with infinitely large periods. In contrast, the insertion of
f induced periodicity via a subcritical Hopf bifurcation at
f≈ 0.25 mSμF−1. Stable autorhythmic action potentials occurred at
f > 0.329 mSμF−1. |
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Keywords: | bifurcation analysis pacemaking I K1 I f inward rectifying current funny current ventricular cell model |
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