Changes in action potential durations brought by inward/outward currents at the early plateau phase: a computational study

Abstract

Action potential duration (APD) of cardiac myocytes are determined by the balance of inward (depolarizing) and outward (hyperpolarizing) currents. In principle, outward currents contribute to shorten and inward currents contribute to prolong APDs. There are cases contradictory to this rule, however, when currents were modified at the early stage of action potentials. We therefore analyzed the effects of inward/outward currents given at this critical phase, using several ventricular action potential models. In classical Beeler-Reuter model (1977), injection of inward current during initial 50msec of action potential shortened, while outward current prolonged APDs. This was primarily produced by the difference of voltage-dependent activation of delayed outward current (undivided I_K). The "reversed" effects of current injection on APD were observed also in Luo-Rudy model (1994). Here, not only different levels of I_Ks activation, but also the amount of Ca²⁺ influx and the Ca²⁺ transient played important roles to determine APDs. This was because [Ca²⁺]_i is an important modulator of cardiac current systems, including I_Ca,L, I_Na-Ca and I_Ks. The "reversed" effects of current injection were even more prominent in our model with a new formulation of I_Ca,L (Ca²⁺-entry dependent inactivation; 2003). Dynamic changes in [Ca²⁺]_i and resultant modulation of current systems play critical roles in cardiac electrophysiology. To progress our understanding on these complex phenomena, further computational as well as experimental investigations are required. [Jpn J Physiol 54 Suppl:S100 (2004)]