Fig. 5.

Simulations of the human atrial action potential in a coupled myocyte/fibroblast system with both I_K(ACh) and I_NP activated. The stimulus current (280 pA, 6 ms) was applied at 1 Hz and a fixed coupling resistance (0.5 nS) was assumed. A The action potential waveform denoted by the solid black trace illustrates the effect of activation of the I_K-ACh in this situation which assumed no intercellular coupling. Note the increased latency, or delay, in the firing of the AP. In this panel the superimposed red trace shows the changes produced by electrotonic coupling to one fibroblast in which I_NP is activated. Note: (i) depolarization of the RMP, and (ii) prolongation of the APD. The dashed line shows the AP waveform assuming no activation of I_K-ACh, in the presence of I_NP in one coupled fibroblast. B shows the corresponding changes in the fibroblast membrane potential V_Fb. Solid black line: control RMP in fibroblast (no coupling). Note that activation of I_NP causes a large depolarization (red trace). The dashed line is the V_FB with I_K(ACh) and I_NP activated. C shows the gap junction current under the three conditions chosen: black trace – resting, control fibroblast; red trace – I_NP activated; dashed trace – both I_K(ACh) and I_NP activated. D Two concentration–response relationships for RMP vs. [ACh]. The black circles (●) show the effect of activation of I_K-ACh on RMP in an uncoupled atrial myocyte (see also Fig. 3). The black squares (■) are analogous data from simulations assuming (i) myocyte–fibroblast coupling (0.5 nS); and (ii) activation of I_NP in the fibroblast.