Effects of amlodipine on native cardiac Na+ channels and cloned alpha-subunits of cardiac Na+ channels

Authors
Inoue, Y Hisatome, I Tsuboi, M Ahmmed, GU Yatsuhashi, T Uchida, K Yamanouchi, Y Santo, Y Miake, J Tanaka, Y Hamada, T Watanabe, M Igawa, O Yoshida, A Shigemasa, C Makita, N Sato, R
Citation
Y. Inoue et al., Effects of amlodipine on native cardiac Na+ channels and cloned alpha-subunits of cardiac Na+ channels, ARZNEI-FOR, 49(5), 1999, pp. 394-397
Citations number
12
Categorie Soggetti
Pharmacology & Toxicology
Journal title
ARZNEIMITTEL-FORSCHUNG-DRUG RESEARCH
ISSN journal
00044172 → ACNP
Volume
49
Issue
5
Year of publication
1999
Pages
394 - 397
Database
ISI
SICI code
0004-4172(199905)49:5<394:EOAONC>2.0.ZU;2-L
Abstract
The inhibitory effects of amlodipine besilate (CAS 11470-99-6) on the nativ e Na+ current (I-Na) and cloned human cardiac Na+ channel alpha subunit (hH 1) were studied by whole cell patch clamp techniques. Amlodipine produced tonic block of I-Na in a concentration- and holding pot ential (HP)dependent manner with hyperpolarization of h(infinity). Amlodipi ne produced phasic blockade of I-Na, which was dependent on HP and pulse du ration. Amlodipine produced tonic blockade of hH1 in a concentration-depend ent manner with 1 : 1 stoichiometry, and phasic blockade of hH1 which was d ependent on the pulse duration. Amlodipine blocked I-Na in a voltage- and f requency-dependent manner via affinity to the resting as well as inactivate d conformations of the a subunit.