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Arzneimittelforschung 1999; 49(5): 394-397
DOI: 10.1055/s-0031-1300433
Cardiac Drugs · Cardiac Stimulants · Coronary Drugs
Editio Cantor Verlag Aulendorf (Germany)

Effects of Amlodipine on Native Cardiac Na+ Channels and Cloned α-Subunits of Cardiac Na+ Channels

Yoshiaki Inoue
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Ichiro Hisatome
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Mariko Tsuboi
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Gias U Ahmmed
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Toru Yatsuhashi
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Kazuhiko Uchida
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Yumi Yamanouchi
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Yuka Santo
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Junichiro Miake
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Yasunori Tanaka
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Toshihiro Hamada
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Masashi Watanabe
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Osamu Igawa
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Akio Yoshida
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Chiaki Shigemasa
a   First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan
,
Naomasa Makita
b   Division of Cardiology, Department of Medicine, Hokkaido University Faculty of Medicine, Sapporo, Japan
,
Ryoichi Sato
c   Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School”, Chicago, Illinois, USA
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Publikationsverlauf

Publikationsdatum:
28. Dezember 2011 (online)

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Summary

The inhibitory effects of amlodipine besilate (CAS 11470-99-6) on the native Na+ current (INa) and cloned human cardiac Na+ channel a subunit (hH1) were studied by whole cell patch clamp techniques.

Amlodipine produced tonic block of INa in a concentration- and holding potential (HP)- dependent manner with hyperpolarization of Amlodipine produced phasic blockade of INa, which was dependent on HP and pulse duration. Amlodipine produced tonic blockade of hH1 in a concentration-dependent manner with 1 : 1 stoichiometry, and phasic blockade of hH1 which was dependent on the pulse duration. Amlodipine blocked INa in a voltage- and frequency-dependent manner via affinity to the resting as well as inactivated conformations of the α subunit.

Zusammenfassung

Wirkungen von Amlodipin auf native kardiale Na+-Kanäle und geklonte Untereinheiten von kardialen Na+-Kanälen

Die hemmende Wirkungen von Amlodipine-Besilat (CAS 11470-99-6) auf native Na+-Ströme (INa) und geklonte menschliche kardiale Na+-Kanal-Untereinheiten (hH 1) wurden mittels Patch-Clamp-Methode untersucht.

Amlodipin führte dabei zu einer dosis- und Haltepotential (holding potential = HP) abhängigen, tonischen Hemmung der INa und zu einer damit gekoppelten h,-Hyperpolarisation. Amlodipine produzierte außerdem eine dosisabhängige phasische hH1 -Hemmung, sowie eine von der Pulsdauer abhängige phasische hHl-Blockade. Über die Affinität zur Konformation der Untereinheit im Ruhezustand und in der inaktiven Form hemmte Amlodipin die INa sowohl in spannungs- als auch frequenzabhängiger Weise.

Key words

Amlodipine, effect on Na+ currents CAS 11470-99-6 - Na+ channel, a-subunit, cardiac