Effects of amlodipine on native cardiac Na+ channels and cloned alpha-subunits of cardiac Na+ channels.
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.
Inoue
Y
Y
First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan.
Hisatome
I
I
Tsuboi
M
M
Ahmmed
G U
GU
Yatsuhashi
T
T
Uchida
K
K
Yamanouchi
Y
Y
Santo
Y
Y
Miake
J
J
Tanaka
Y
Y
Hamada
T
T
Watanabe
M
M
Igawa
O
O
Yoshida
A
A
Shigemasa
C
C
Makita
N
N
Sato
R
R
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
D002121:Calcium Channel Blockers; D053503:Epithelial Sodium Channels; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D017311:Amlodipine; D013779:Tetrodotoxin