title: Genesis of the monophasic action potential: role of interstitial resistance and boundary gradients.
abstract: The 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 three-dimensional 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.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC 27708-0281, USA.
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Tranquillo
authors.forename: Michael R
authors.initials: MR
authors.lastname: Franz
authors.forename: Björn C
authors.initials: BC
authors.lastname: Knollmann
authors.forename: Alexandra P
authors.initials: AP
authors.lastname: Henriquez
authors.forename: Doris A
authors.initials: DA
authors.lastname: Taylor
authors.forename: Craig S
authors.initials: CS
authors.lastname: Henriquez
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000465:Algorithms; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D004566:Electrodes; D005110:Extracellular Space / Q000502:physiology; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D009206:Myocardium / Q000166:cytology; D009431:Neural Conduction / Q000502:physiology; D010477:Perfusion; D011312:Pressure