Frequency-dependent and independent effects of tetrodotoxin on Vmax in cardiac fibers.
Superfusion with 3 microM tetrodotoxin (TTX) induced both a use-dependent and a frequency-independent depression of the rate rise of the action potential (Vmax) in dog Purkinje and guinea pig ventricular muscle fibers. The recovery from block was fast and exponential with a time constant of 225.4 +/- 7.1 ms in dog Purkinje fibers (n = 6). The onset kinetics of the frequency-dependent Vmax block was rapid, i.e. reached steady state after 3.0 +/- 0.3 beats in guinea pig ventricular muscle (n = 6). The rapid use-dependent interactions with sodium channel make TTX similar to antiarrhythmic drugs with fast kinetics i.e. lidocaine, mexiletine, and tocainide, but unlike antiarrhythmic drugs, TTX-induces a large frequency-independent Vmax block at the same concentrations.
Varró
A
A
Institute for Drug Research Budapest, Hungary.
Nakaya
Y
Y
Elharrar
V
V
Surawicz
B
B
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000502:physiology*; D066298:In Vitro Techniques; D010210:Papillary Muscles / Q000502:physiology*; D011690:Purkinje Fibers / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology*
D013779:Tetrodotoxin