title: Tonic block of the Na+ current in single atrial and ventricular guinea-pig myocytes, by a new antiarrhythmic drug, Ro 22-9194.
abstract: 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.
authors.affiliation: First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hiroe
authors.forename: I
authors.initials: I
authors.lastname: Hisatome
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: G U
authors.initials: GU
authors.lastname: Ahmmed
authors.forename: N
authors.initials: N
authors.lastname: Sasaki
authors.forename: M
authors.initials: M
authors.lastname: Shimoyama
authors.forename: M
authors.initials: M
authors.lastname: Tsuboi
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: I
authors.initials: I
authors.lastname: Manabe
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: A
authors.initials: A
authors.lastname: Ohtahata
authors.forename: T
authors.initials: T
authors.lastname: Kinugawa
authors.forename: K
authors.initials: K
authors.lastname: Ogino
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: R
authors.initials: R
authors.lastname: Sato
mesh_terms: 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
chemical_list: D000889:Anti-Arrhythmia Agents; D011725:Pyridines; D026941:Sodium Channel Blockers; C066993:Ro 22-9194