Genesis of the monophasic action potential: role of interstitial resistance and boundary gradients

Abstract

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...

Monophasic action potentials generated by bidomain modeling as a tool for detecting cardiac repolarization times

“…An almost PD volume was obtained experimentally by contact pressure or by KCl injection in a small PD volume of the cardiac slab H, holding the TAP in such a region to some fixed depolarized value. Modeling studies of the PD volume and the close bipolar MAP can be found elsewhere (51,52). In our model, we obtained a PD volume by assigning the extracellular potassium concentration equal to the intracellular one, so that the reversal potentials E K1 and EKp in the LR1 model are set to zero in the PD volume (37).…”

“…Previously, the origin and interpretation of the HMAP waveform have been the subject of a controversy concerning which electrode is responsible for the genesis of MAPs. These controversial issues regarding the origin and interpretation of the MAP and HMAP signal morphology are beyond the scope of this paper, and we refer interested readers to other studies (11,18,26,28,29,34,35,51,53,56) for a discussion of these issues.…”

Mathematical Modeling and Simulation of Ventricular Activation Sequences: Implications for Cardiac Resynchronization Therapy

“…The difference between these potentials yields a signal that resembles an action potential, a signal that is normally measured between the intracellular and extracellular potentials at the same location. The precise mechanism of the depolarization and the degree to which the cells depolarize are uncertain, but the physics behind the MAP are well understood, and its working has been illustrated in several computer model studies [110, 119, 120]. …”

Stable time integration suppresses unphysical oscillations in the bidomain model

“…For example, the forward Euler (FE) method has been used frequently; see e.g., Muzikant et al [5], Sambelashvili and Efimov [6], ten Tusscher and Panfilov [7], and Tranquillo et al [8]. An investigation of the stability of FE applied to the bidomain model was performed in Puwal and Roth [9].…”