IONIC MECHANISMS UNDERLYING HUMAN ATRIAL ACTION-POTENTIAL PROPERTIES - INSIGHTS FROM A MATHEMATICAL-MODEL

The mechanisms underlying many important properties of the human atria l action potential (AP) are poorly understood. Using specific formulat ions of the K+, Na+, and Ca2+ currents based on data recorded from hum an 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 inh ibition, and variations in transient outward current amplitude in a fa shion similar to experimental recordings. Rate-dependent adaptation of AP duration, an important determinant of susceptibility to atrial fib rillation, was attributable to incomplete L-type Ca2+ current recovery from inactivation and incomplete delayed rectifier current deactivati on at rapid rates. Experimental observations of variable AP morphology could be accounted for by changes in transient outward current densit y, as suggested experimentally. We conclude that this mathematical mod el of the human atrial AP reproduces a variety of observed AP behavior s and provides insights into the mechanisms of clinically important AP properties.