title: Effects of amlodipine on native cardiac Na+ channels and cloned alpha-subunits of cardiac Na+ channels.
abstract: The inhibitory effects of amlodipine besilate (CAS 11470-99-6) on the native Na+ current (INa) and cloned human cardiac Na+ channel alpha 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 H infinity. 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 alpha subunit.
authors.affiliation: First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: I
authors.initials: I
authors.lastname: Hisatome
authors.forename: M
authors.initials: M
authors.lastname: Tsuboi
authors.forename: G U
authors.initials: GU
authors.lastname: Ahmmed
authors.forename: T
authors.initials: T
authors.lastname: Yatsuhashi
authors.forename: K
authors.initials: K
authors.lastname: Uchida
authors.forename: Y
authors.initials: Y
authors.lastname: Yamanouchi
authors.forename: Y
authors.initials: Y
authors.lastname: Santo
authors.forename: J
authors.initials: J
authors.lastname: Miake
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Hamada
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: O
authors.initials: O
authors.lastname: Igawa
authors.forename: A
authors.initials: A
authors.lastname: Yoshida
authors.forename: C
authors.initials: C
authors.lastname: Shigemasa
authors.forename: N
authors.initials: N
authors.lastname: Makita
authors.forename: R
authors.initials: R
authors.lastname: Sato
mesh_terms: D000465:Algorithms; D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003001:Cloning, Molecular; D053503:Epithelial Sodium Channels; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011487:Protein Conformation; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D053503:Epithelial Sodium Channels; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D017311:Amlodipine; D013779:Tetrodotoxin