Discontinuous cardiac conduction: coupling real cells to model cells

The authors have developed the “coupling clamp” technique in which an isolated cardiac myocyte is coupled to either another isolated myocyte or to a real-time simulation of a cardiac action potential (AP). This method precisely controls the coupling conductance, G_C, between the cells. Additionally, the membrane properties of either cell can be altered. Thus a wide variety of questions regarding modulation of propagation can be tested. By coupling a guinea pig ventricular cell and a Luo-Rudy AP model over a range of G_c, the authors found the critical value of G_c required for propagation was increased by nifedipine (6.8±0.1 nS in control vs. 8.8±0.2 nS, p<0.0001) and decreased by isoproterenol (5.3±0.2 nS, p<0.001) (mean±SEM). Thus with less calcium current (I_Ca) available (blocked by nifedipine), more conductance was required for propagation. Additionally, with enhanced I_Ca (stimulation by isoproterenol) less conductance was required for propagation, thereby demonstrating the importance of I_Ca in maintaining propagation at low values of G_c. The authors extended their coupling clamp technique to include the ability to couple a real cell to an array of 49 model cells. They coupled atrioventricular node cells to an array of either ventricular or atrial model cells and varied the size of the focus cell and the conductance of the array. For all G_c tested, the critical size of the focus was smaller for activation of an atrial versus a ventricular array. The major differences between activation of the arrays are due to the higher membrane resistance (lower I_K1) of the atrial versus ventricular cells