| Title: | EFFECTS OF INWARD/OUTWARD CURRENT INJECTION AT THE EARLY PLATEAU PHASE ON CARDIAC ACTION POTENTIAL DURATIONS: A COMPUTATIONAL STUDY |
| DOI No: | 10.1142/9789812702234_0024 |
| Source: | ADVANCES IN ELECTROCARDIOLOGY 2004 (pp 103-107)
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| Author(s): | YUJI HIRANO
Dep't of Cardiovascular Diseases, MRI, Tokyo Medical and Dental University 1-5-45 Yushima, Bunkyo-ku Tokyo 113-8510, Japan
MASAYASU HIRAOKA
present address: Labour Insurance Appeal Committee, Ministry of Health, Labour and Welfare 1-5-32, Shibakouen, Minato-ku, Tokyo 105-0011, Japan
Dep't of Cardiovascular Diseases, MRI, Tokyo Medical and Dental University 1-5-45 Yushima, Bunkyo-ku Tokyo 113-8510, Japan
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| Abstract: | When currents were modified at the early stage of action potentials, the effects of inward (depolarizing) and outward (hyperpolarizing) currents on action potential duration (APD) are not straightforward (Greenstein et al. 2000, Wehrens et al. 2000). To obtain theoretical insight into this complexity, we analyzed effects of inward/outward current injection during early repolarization phase using various cardiac action potential models. In Beeler-Reuter model, injection of inward current during initial 50msec of action potential shortened, while outward current prolonged APDs. This "reversed effect" was primarily produced by different extent of voltage-dependent activation of delayed outward K+ current, Ik. The "reversed" effects of current injection on APD were observed also in Luo-Rudy model. Here, not only difference in IKs activation, but also Ca2+ influx and intracellular Ca2+ dynamics played important roles. This was because [Ca2+]i is an important modulator of various current systems, including ICa,L, IKs and INa-Ca. The "reversed" effects of current injection were even more prominent in our model with a new formulation of ICa,L, (Ca2+-entry dependent inactivation; Hirano and Hiraoka, 2003). In both models, when the current amplitude of INa-ca was reduced, the extent of APD modulation produced by inward/outward current injection was diminished. 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 experimental and computational investigations are required. |
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