title: Influence of extracellular H+ and Ca2+ on Ro 22-9194-induced block of sodium current in cardiac myocytes.
abstract: 1. Ro 22-9194 reduced the Na current in ventricular myocytes in either a tonic block or phasic block manner. 2. Ro 22-9194 had a higher affinity to the inactivated state (Kdi = 10.3 microM) than to the rested state (Kdrest = 180 microM). 3. Extracellular acidification enhanced the tonic block but reduced the phasic block. 4. Elevation of extracellular Ca2+ inhibited the enhancing effects of extracellular acidification. 5. These findings suggest that Ro 22-9194 strongly inhibits Na+ channels of the ventricular myocytes of the diseased hearts, characterized by the depolarized cell membranes and by acid conditions.
authors.affiliation: First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Hisatome
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: N
authors.initials: N
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Hiroe
authors.forename: G U
authors.initials: GU
authors.lastname: Ahmmed
authors.forename: M
authors.initials: M
authors.lastname: Tsuboi
authors.forename: I
authors.initials: I
authors.lastname: Manabe
authors.forename: T
authors.initials: T
authors.lastname: Suga
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: A
authors.initials: A
authors.lastname: Ohtahara
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: M
authors.initials: M
authors.lastname: Saito
authors.forename: R
authors.initials: R
authors.lastname: Sato
authors.forename: C
authors.initials: C
authors.lastname: Shigemasa
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009129:Muscle Tonus / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology*; D012964:Sodium / Q000502:physiology*; D016276:Ventricular Function
chemical_list: D000889:Anti-Arrhythmia Agents; D011725:Pyridines; C066993:Ro 22-9194; D012964:Sodium; D002118:Calcium