Atria Selective Prolongation by NIP-142, an Antiarrhythmic Agent, of Refractory Period and Action Potential Duration in Guinea Pig Myocardium

DOI Web Site PubMed 被引用文献11件 参考文献53件
  • Matsuda Tomoyuki
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences Biological Research Laboratories, Nissan Chemical Industries, Ltd.
  • Takeda Kentaro
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences
  • Ito Mie
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences
  • Yamagishi Reiko
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences
  • Tamura Miku
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences
  • Nakamura Hideki
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences
  • Tsuruoka Noriko
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences
  • Saito Tomoaki
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences
  • Masumiya Haruko
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences
  • Suzuki Takeshi
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences School of Material Science, Japan Advanced Institute of Science and Technology
  • Iida-Tanaka Naoko
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences Department of Food Science, Otsuma Woman's University
  • Itokawa-Matsuda Maho
    Biological Research Laboratories, Nissan Chemical Industries, Ltd.
  • Yamashita Toru
    Biological Research Laboratories, Nissan Chemical Industries, Ltd.
  • Tsuruzoe Nobutomo
    Biological Research Laboratories, Nissan Chemical Industries, Ltd.
  • Tanaka Hikaru
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences
  • Shigenobu Koki
    Department of Pharmacology, Toho University School of Pharmaceutical Sciences

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NIP-142 is a novel benzopyran compound that was shown to prolong the atrial effective refractory period and terminate experimental atrial fibrillation in the dog. In the present study, we examined the effects of NIP-142 on isolated guinea pig myocardium and on the G-protein-coupled inwardly rectifying potassium channel current (acetylcholine-activated potassium current; IKACh) expressed in Xenopus oocytes. NIP-142 (10 and 100 μM) concentration-dependently prolonged the refractory period and action potential duration in the atrium but not in the ventricle. E-4031 and 4-aminopyridine prolonged action potential duration in both left atrium and right ventricle. Prolongation by NIP-142 of the atrial action potential duration was observed at stimulation frequencies between 0.5 and 5 Hz. In contrast, the prolongation by E-4031 was not observed at higher frequencies. Tertiapin, a blocker of IKACh, prolonged action potential duration in the atrium but not in the ventricle. NIP-142 completely reversed the carbachol-induced shortening of atrial action potential duration. NIP-142 (1 to 100 μM), as well as tertiapin (0.1 to 100 nM), concentration-dependently blocked IKACh expressed in Xenopus oocytes; the blockade by NIP-142 was not affected by membrane voltage. In conclusion, NIP-142 was shown to prolong atrial refractory period and action potential duration through blockade of IKACh which may possiblly explain its previously described antiarrhythic activity. NIP-142 has pharmacological properties that are different from classical class III antiarrhythmic agents such as atria specificity and lack of reverse frequency dependence, and thus appears promising for the treatment of supraventricular arrhythmia.<br>

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