Fig. 4.

Action potential simulations made on the basis of a model system consisting of one human atrial myocyte (incorporating I_K(ACh) at 10 nM) coupled to a one fibroblast through a G_gap of 0.5 nS. (A) Comparison of AP waveforms during a stimulation protocol employing a 6 ms 280 pA stimulus current applied a basic cycle length of 1 s (1 Hz). Note that in the uncoupled myocyte when I_K(ACh) (black solid trace) is activated there is an activation delay. In contrast, since coupling the ACh-treated myocyte to a fibroblast depolarizes the RMP, application of ACh does not result in any activation delay in this situation (red line). Note that the coupled myocyte which is not treated with ACh has the most depolarized RMP, and a relative prolongation of APD (black dashed line). (B) Comparison of the electrotonic changes in the membrane potential of the fibroblast (V_Fb) as a result of coupling to one atrial myocyte. Solid black line represents the intrinsic or control RMP of the uncoupled fibroblast. Coupling to a myocyte (either with or without I_K(ACh)) results in a similar hyper-polarization of the fibroblast RMP. (C) Gap junctional current, Igap. Note that coupling one fibroblast to one myocyte either with or without I_K(ACh), results in a similar I_gap. (D) Concentration–response relationship for [ACh] vs. RMP in both the uncoupled (●) and coupled (◊) human atrial myocyte. The ligand-gated current, I_K(ACh), was active during each of these simulations in the myocyte model (black circles and diamonds, respectively).