Stretch-induced alternation of cardiac action potential duration: a study of computer simulations

Abstract

Stretch-activated channels (SACs) have been considered as one of the possible modulators on the mechanisms of mechano-electrical feedback (MEF) in the heart. With the abilities to modulate action potential duration (APD) during the systolic period and to trigger action potentials directly by diastolic stretch, SACs could play an important role on stretch-induced arrhythmias. The objective of this present study was to explore the impact of SACs on modulating action potential duration by different kinds of stretches including slow ramp stretch and quick step stretch. A mathematical model of ventricular cells based on Noble's descriptions was constructed with the addition of the time-independent model of SACs. The differential equations involved in the cell model were solved numerically by the algorithm of Runge-Kutta-Fehlberg with adaptive time steps. The simulation results indicated the following. First, the action potential duration was shortened 3% to 8% without crossover with non-stretched action potential under various slow ramp stretches. Second, by quick step stretch, the lengthening of action potential duration was observed with crossover with non-stretched action potential at certain membrane potentials. The crossover potentials varied from -18 mV to -50 mV with increased sustained quick step stretch from sarcomere length 1.1 to 2.3. Third, the presence of a specific time window allowed shortening action potential duration if quick step stretch applied inside. The window duration was increased with the amplitude of stretch. It was concluded that SACs activated by ramp stretch could lead to the shortening of action potential duration independent of the activation timing. However, the shortening or lengthening of action potential duration was determined by activation timing under quick step stretch.