Tonic block of the Na+ current in single atrial and ventricular guinea-pig myocytes, by a new antiarrhythmic drug, Ro 22-9194.
Ro 22-9194 reduced the Na+ current in the atrial myocytes as well as ventricular myocytes in a tonic block fashion. Ro 22-9194 had a higher affinity to the inactivated state Na+ channels (KdI = 3.3 microM in atrial myocytes, KdI = 10.3 microM in ventricular myocytes) than to those in the rested state (KdR = 91 microM in atrial myocytes, KdR = 180 microM in ventricular myocytes), which indicated that Ro 22-9194 had a higher affinity to the Na+ channels in atrial myocytes than in ventricular myocytes. Ro 22-9194 shifted the inactivation curve in the hyperpolarized direction in both atrial and ventricular myocytes. These findings suggest that Ro 22-9194 more strongly inhibited the Na+ channel of the atrial myocytes of the diseased hearts with the depolarized membranes potentials than the Na+ channels in ventricular myocytes.
Hiroe
K
K
First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan.
Hisatome
I
I
Tanaka
Y
Y
Ahmmed
G U
GU
Sasaki
N
N
Shimoyama
M
M
Tsuboi
M
M
Inoue
Y
Y
Manabe
I
I
Yamamoto
Y
Y
Ohtahata
A
A
Kinugawa
T
T
Ogino
K
K
Igawa
O
O
Yoshida
A
A
Shigemasa
C
C
Sato
R
R
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology*; D026941:Sodium Channel Blockers
D000889:Anti-Arrhythmia Agents; D011725:Pyridines; D026941:Sodium Channel Blockers; C066993:Ro 22-9194