Influence of extracellular H+ and Ca2+ on Ro 22-9194-induced block of sodium current in cardiac myocytes.
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.
Hisatome
I
I
First Department of Medicine, Tottori University Faculty of Medicine, Yonago, Japan.
Tanaka
Y
Y
Sasaki
N
N
Hiroe
K
K
Ahmmed
G U
GU
Tsuboi
M
M
Manabe
I
I
Suga
T
T
Yamamoto
Y
Y
Ohtahara
A
A
Kinugawa
T
T
Ogino
K
K
Igawa
O
O
Yoshida
A
A
Saito
M
M
Sato
R
R
Shigemasa
C
C
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
D000889:Anti-Arrhythmia Agents; D011725:Pyridines; C066993:Ro 22-9194; D012964:Sodium; D002118:Calcium