title: A mathematical model of electrophysiological activity in a bullfrog atrial cell.
abstract: We have developed a model of cardiac atrial electrical activity based on voltage-clamp measurements obtained from single cells isolated from the bullfrog atrium. These measurements have allowed us to simulate a number of processes thought to be important in action potential initiation, repolarization, and the excitation-contraction (EC) coupling process. In this atrial model, the cell membrane contains both channel-mediated (Na+, Ca2+, inward rectifier K+, delayed rectifier K+, linear background leak) and transporter-mediated (Na(+)-K+ pump, Na(+)-Ca2+ exchanger, Ca2+ pump) currents. The cell is surrounded extracellularly by a diffusion-limited space. The intracellular volume contains Ca2(+)-binding proteins (calmodulin, troponin). The model makes several important predictions. 1) Incomplete inactivation of the Ca2+ current provides an inward current the maintains the plateau of the action potential. 2) Activation of the delayed rectifier K+ current initiates repolarization. 3) Due to Ca2+ buffering by myoplasmic proteins the Na(+)-Ca2+ exchanger current is relatively small and has little influence on repolarization. 4) The Na(+)-K+ pump current does not play a major role in repolarization. 5) K+ accumulation and Ca2+ depletion may occur in the extracellular spaces. 6) Modulation of EC coupling is governed by interactions between the myoplasmic Ca2(+)-binding proteins; specifically, the inotropic "positive staircase effect" may be explained by interactions between Ca2+ and Mg2+ at a competitive binding site on troponin. When considered in conjunction with the results of our model of primary pacemaking in the sinus venosus [Rasmusson et al., Am. J. Physiol. 259 (Heart Circ. Physiol. 28): H352-H369, 1990], this atrial model shows how the presence or absence of certain transmembrane currents can change action potential characteristics and consequently alter the relative influence of the various transporter-mediated and channel-mediated currents.
authors.affiliation: Department of Electrical and Computer Engineering, Rice University, Houston, Texas 77251-1892.
authors.forename: R L
authors.initials: RL
authors.lastname: Rasmusson
authors.forename: J W
authors.initials: JW
authors.lastname: Clark
authors.forename: W R
authors.initials: WR
authors.lastname: Giles
authors.forename: K
authors.initials: K
authors.lastname: Robinson
authors.forename: R B
authors.initials: RB
authors.lastname: Clark
authors.forename: E F
authors.initials: EF
authors.lastname: Shibata
authors.forename: D L
authors.initials: DL
authors.lastname: Campbell
mesh_terms: D000200:Action Potentials; D000818:Animals; D001001:Anura; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000502:physiology; D004594:Electrophysiology; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D007477:Ions; D008433:Mathematics; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D007477:Ions; D012964:Sodium; D011188:Potassium; D002118:Calcium