The gap junction connecting cardiac myocytes is voltage and time dependent. This simulation study investigated the effects of dynamic gap junctions on both the shape and conduction velocity of a propagating action potential. The dynamic gap junction model is based on that described by Vogel and Weingart (J. Physiol. (Lond.). 1998, 510:177-189) for the voltage- and time-dependent conductance changes measured in cell pairs. The model assumes that the conductive gap junction channels have four conformational states. The gap junction model was used to couple 300 cells in a linear strand with membrane dynamics of the cells defined by the Luo-Rudy I model. The results show that, when the cells are tightly coupled (6700 channels), little change occurs in the gap junction resistance during propagation. Thus, for tight coupling, there are negligible differences in the waveshape and propagation velocity when comparing the dynamic and static gap junction representations. For poor coupling (85 channels), the gap junction resistance increases 33 MOmega during propagation. This transient change in resistance resulted in increased transjunctional conduction delays, changes in action potential upstroke, and block of conduction at a lower junction resting resistance relative to a static gap junction model. The results suggest that the dynamics of the gap junction enhance cellular decoupling as a possible protective mechanism of isolating injured cells from their neighbors.

of the monophasic action potential: role of interstitial resistance and boundary gradients. Am J Physiol Heart Circ Physiol 286: H1370-H1381, 2004. First published December 4, 2003 10.1152/ajpheart.00803.2003The extracellular potential at the site of a mechanical deformation has been shown to resemble the underlying transmembrane action potential, providing a minimally invasive way to access membrane dynamics. The biophysical factors underlying the genesis of this signal, however, are still poorly understood. With the use of data from a recent experimental study in a murine heart, a threedimensional anisotropic bidomain model of the mouse ventricular free wall was developed to study the currents and potentials resulting from the application of a point mechanical load on cardiac tissue. The applied pressure is assumed to open nonspecific pressure-sensitive channels depolarizing the membrane, leading to monophasic currents at the electrode edge that give rise to the monophasic action potential (MAP). The results show that the magnitude and the time course of the MAP are reproduced only for certain combinations of local or global intracellular and interstitial resistances that form a resting tissue length constant that, if applied over the entire domain, is smaller than that required to match the wave speed. The results suggest that the application of pressure not only causes local depolarization but also changes local tissue properties, both of which appear to play a critical role in the genesis of the MAP. cardiac inhomogeneities; extracellular potentials; computer simulation EXTRACELLULARLY RECORDED SIGNALS, produced by applying a point mechanical load to the myocardium, have been shown to resemble the underlying transmembrane action potential (TAP) and thus have been used to gain information about the electrophysiology of cardiac muscle when intracellular microelectrode recordings are not possible or too challenging to perform. In the beating heart, these extracellular signals, generally termed monophasic action potentials (MAPs), are widely used to measure the effects of drugs and exogenous stimulation and to gain insight into the cellular origin of arrhythmias (7). Whereas MAPs and TAPs have been compared in several studies (9,14,15), the biophysical connection between the two signals is not completely understood (7,18,26,36).Several biophysical models have been created to elucidate the biophysical basis of the MAP produced by contact pressure. Malden and Henriquez (24,25) and later Trayanova et al. (34), building on the early work of Hirsch et al. (13), modeled the region under the electrode as passive and not capable of generating an action potential. These models showed that large current sources form at the periphery of the inhomogeneity due to the large potential gradient created between the region of contact and the adjacent myocardium. During plateau, these sources dominate the surrounding sources and have monophasic time courses that follow the underlying TAPs. While the extracellular potentials abo...

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