Mechanism for action potential alternans: the interplay between L-type calcium current and transient outward current.
BACKGROUND
The ionic mechanisms underlying action potential duration alternans are not established.


OBJECTIVE
The purpose of this study was to explore the mechanisms underlying action potential alternans.


METHODS
Computer simulations were performed using a model of a single ischemic myocyte. To emulate ischemia, extracellular potassium was raised to 10 mM, L-type calcium channel conductance was decreased, and the conductivity of the transient outward current I(to)was varied.


RESULTS
Alternans occurred at basic cycle lengths between 350 and 1,800 ms. The alternans resulted from the interplay of the recovery kinetics of the calcium and transient outward current inactivation gates. Depending on the diastolic interval, the transient outward current was sufficiently strong and calcium current sufficiently weak to result in the abolition of the action potential plateau and thus in an abbreviated action potential. The inactivation and recovery kinetics of the inactivation gates were such that calcium current was relatively stronger than transient outward current after an abbreviated action potential. The subsequent action potential was long because calcium current was sufficiently large to restore the action potential plateau dome after the partial repolarization caused by the transient outward current. The long-short pattern repeated indefinitely. This alternans mechanism explains how 2:1 patterns can evolve into 3:1 patterns, as observed in at least one experiment, as ischemia progresses and calcium current diminishes.


CONCLUSIONS
Computer simulations and basic theory suggest that the interplay between L-type calcium and transient outward currents causes at least one type of alternans.
Hopenfeld
Bruce
B
National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Drive, MSC 1061, Bethesda, MD 20892, USA. hopenfeldb@mail.nih.gov
D000200:Action Potentials / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D003198:Computer Simulation; D004594:Electrophysiology; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology
D015220:Calcium Channels; D007473:Ion Channels; D015222:Sodium Channels