Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model.
The mechanisms underlying many important properties of the human atrial action potential (AP) are poorly understood. Using specific formulations of the K+, Na+, and Ca2+ currents based on data recorded from human atrial myocytes, along with representations of pump, exchange, and background currents, we developed a mathematical model of the AP. The model AP resembles APs recorded from human atrial samples and responds to rate changes, L-type Ca2+ current blockade, Na+/Ca2+ exchanger inhibition, and variations in transient outward current amplitude in a fashion similar to experimental recordings. Rate-dependent adaptation of AP duration, an important determinant of susceptibility to atrial fibrillation, was attributable to incomplete L-type Ca2+ current recovery from inactivation and incomplete delayed rectifier current deactivation at rapid rates. Experimental observations of variable AP morphology could be accounted for by changes in transient outward current density, as suggested experimentally. We conclude that this mathematical model of the human atrial AP reproduces a variety of observed AP behaviors and provides insights into the mechanisms of clinically important AP properties.
Research Center, Montreal Heart Institute, Montreal, Quebec H1T 1C8, Canada.
M
M
Courtemanche
R J
RJ
Ramirez
S
S
Nattel
D000200:Action Potentials / Q000502:physiology*; D016275:Atrial Function / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D006801:Humans; D007700:Kinetics; D008955:Models, Cardiovascular; D008962:Models, Theoretical; D009206:Myocardium / Q000166:cytology; D015221:Potassium Channels / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger