Mechanisms of rectified gap junctional coupling enhancing pacemaking activity of biologically engineered pacemaker cells

Figures

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  Fig. 1. Effect of W-REC on pacemaking states in idealised cardiac tissue. A Average minimum numbers needed to drive 100 VM cells under different DPMs. B Pacemaking states of cardiac tissue under different DPM2VM and DVM2PM percentages. C States of electrical excitation waves under different DPMs and DVM2PM percentages of VM’s original value. White: No persistent spontaneous pacemaking; Green: Automaticity without propagation; Yellow: Automaticity with conduction block; Blue: Spontaneous pacemaking and propagation. D Diagrams of the initiation and conduction of membrane potential plotted in space-time for (DPMs, DVM2PM) = (20%, 30%) ((i)), (2%, 40%) ((ii)), (2%, 35%) ((iii)) and (2%, 20%) ((iv)). The red line marks the boundary between PM and VM tissue.

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  Fig. 2. Mechanism of automatic electrical signal propagation from PM to VM. A The definition of Iadj, Iin and Iout. To PM cells, Iadj is defined as the sum of currents from neighbouring cells to a single PM cell, including the current flowing from the PM cells to the present PM cell (depolarising current, Iin) and the current flowing from the VM cell to the present PM cell (repolarising current, Iout). B–D V, Iadj and Iout of the PM neighbouring VM tissue when (DPM2VM, DVM2PM) = (2%, 17%), (2%, 18%), (2%, 19%), respectively.

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  Fig. 3. Effect of nonlinear REC on the bio-pacemaker performance. A The relationship between Vgap and the diffusion coefficient between PM and VM (DP) in original and modified value with (A1, Vh1) is (0.18, 1) and (0.5, −5), respectively. B Space-time plots of action potentials on the 1D strand of the cardiac tissue model under original and modified nonlinear DP, as shown in (A). From top to bottom, the vertical column includes pacemaker cells (PMs), endocardial cells (ENDO), midmyocardial cells (MCELL) and epicardial cells (EPI). C Pacemaking states of cardiac tissue with different nonlinear REC parameters. The blue cross marks the cases of no normal electrical signal in tissue. The red circle indicates that the pacemaking wave can be propagated into VMs. The yellow asterisk marks the original parameters.

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  Fig. 4. Effect of bio-pacemaker’s spatial distribution on its driving capacity. A Initial potential mappings of cardiac tissue under normal electrical coupling conditions with different spatial distributions. B Initial potential mappings of cardiac tissue under W-REC conditions with different spatial distributions. C The driving capacity of bio-pacemakers under various spatial distributions and electrical coupling modes.

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  Fig. 5. Effect of bio-pacemaker location on the synchrony of cardiac tissue. A Potential mappings of cardiac tissue implanted with an isolated bio-pacemaker under W-REC conditions. B Location of bio-pacemaker in an actual ventricular tissue model. C Pacemaking properties at different pacemaker locations.

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  Fig. 6. Spatial distribution of cardiac tissue model and illustration of rectified intercellular electrical coupling structure. A Illustration of diffusion coefficient (D) in a full side-to-side coupling model. B Spatial distribution of cells in a full side-to-side coupling model, an embedded model and an isolated model. Inset: The value of D between PM and VM.