Atria selective prolongation by NIP-142, an antiarrhythmic agent, of refractory period and action potential duration in guinea pig myocardium

Tomoyuki Matsuda, Kentaro Takeda, Mie Ito, Reiko Yamagishi, Miku Tamura, Hideki Nakamura, Noriko Tsuruoka, Tomoaki Saito, Haruko Masumiya, Takeshi Suzuki, Naoko Iida-Tanaka, Maho Itokawa-Matsuda, Toru Yamashita, Nobutomo Tsuruzoe, Hikaru Tanaka, Koki Shigenobu

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)33-40
Number of pages8
JournalJournal of Pharmacological Sciences
Volume98
Issue number1
DOIs
Publication statusPublished - 2005 May
Externally publishedYes

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Action Potentials
Myocardium
Guinea Pigs
Xenopus
Heart Ventricles
Oocytes
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Benzopyrans
NIP142
4-Aminopyridine
Carbachol
Heart Atria
Atrial Fibrillation
Acetylcholine
Cardiac Arrhythmias
Potassium
Pharmacology
Dogs
Membranes

Keywords

  • Action potential duration
  • Antiarrhythmic agent
  • NIP-142
  • Refractory period

ASJC Scopus subject areas

  • Pharmacology

Cite this

Atria selective prolongation by NIP-142, an antiarrhythmic agent, of refractory period and action potential duration in guinea pig myocardium. / Matsuda, Tomoyuki; Takeda, Kentaro; Ito, Mie; Yamagishi, Reiko; Tamura, Miku; Nakamura, Hideki; Tsuruoka, Noriko; Saito, Tomoaki; Masumiya, Haruko; Suzuki, Takeshi; Iida-Tanaka, Naoko; Itokawa-Matsuda, Maho; Yamashita, Toru; Tsuruzoe, Nobutomo; Tanaka, Hikaru; Shigenobu, Koki.

In: Journal of Pharmacological Sciences, Vol. 98, No. 1, 05.2005, p. 33-40.

Research output: Contribution to journalArticle

Matsuda, T, Takeda, K, Ito, M, Yamagishi, R, Tamura, M, Nakamura, H, Tsuruoka, N, Saito, T, Masumiya, H, Suzuki, T, Iida-Tanaka, N, Itokawa-Matsuda, M, Yamashita, T, Tsuruzoe, N, Tanaka, H & Shigenobu, K 2005, 'Atria selective prolongation by NIP-142, an antiarrhythmic agent, of refractory period and action potential duration in guinea pig myocardium', Journal of Pharmacological Sciences, vol. 98, no. 1, pp. 33-40. https://doi.org/10.1254/jphs.FPJ04045X
Matsuda, Tomoyuki ; Takeda, Kentaro ; Ito, Mie ; Yamagishi, Reiko ; Tamura, Miku ; Nakamura, Hideki ; Tsuruoka, Noriko ; Saito, Tomoaki ; Masumiya, Haruko ; Suzuki, Takeshi ; Iida-Tanaka, Naoko ; Itokawa-Matsuda, Maho ; Yamashita, Toru ; Tsuruzoe, Nobutomo ; Tanaka, Hikaru ; Shigenobu, Koki. / Atria selective prolongation by NIP-142, an antiarrhythmic agent, of refractory period and action potential duration in guinea pig myocardium. In: Journal of Pharmacological Sciences. 2005 ; Vol. 98, No. 1. pp. 33-40.
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AU - Takeda, Kentaro

AU - Ito, Mie

AU - Yamagishi, Reiko

AU - Tamura, Miku

AU - Nakamura, Hideki

AU - Tsuruoka, Noriko

AU - Saito, Tomoaki

AU - Masumiya, Haruko

AU - Suzuki, Takeshi

AU - Iida-Tanaka, Naoko

AU - Itokawa-Matsuda, Maho

AU - Yamashita, Toru

AU - Tsuruzoe, Nobutomo

AU - Tanaka, Hikaru

AU - Shigenobu, Koki

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N2 - 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.

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