title: Basis for tetrodotoxin and lidocaine effects on action potentials in dog ventricular myocytes.
abstract: We studied the effects of tetrodotoxin (TTX) and lidocaine on transmembrane action potentials and ionic currents in dog isolated ventricular myocytes. TTX (0.1-1 x 10(-5) M) and lidocaine (0.5-2 x 10(-5) M) decreased action potential duration, but only TTX decreased the maximum rate of depolarization (Vmax). Both TTX (1-2 x 10(-5) M) and lidocaine (2-5 x 10(-5) M) blocked a slowly inactivating toward current in the plateau voltage range. The voltage- and time-dependent characteristics of this current are virtually identical to those described in Purkinje fibers for the slowly inactivating inward Na+ current. In addition, TTX abolished the outward shift in net current at plateau potentials caused by lidocaine alone. Lidocaine had no detectable effect on the slow inward Ca2+ current and the inward K+ current rectifier, Ia. Our results indicate that 1) there is a slowly inactivating inward Na+ current in ventricular cells similar in time, voltage, and TTX sensitivity to that described in Purkinje fibers; 2) both TTX and lidocaine shorten ventricular action potentials by reducing this slowly inactivating Na+ current; 3) lidocaine has no additional actions on other ionic currents that contribute to its ability to abbreviate ventricular action potentials; and 4) although both agents shorten the action potential by the same mechanism, only TTX reduces Vmax. This last point suggests that TTX produces tonic block of Na+ current, whereas lidocaine may produce state-dependent Na+ channel block, namely, blockade of Na+ current only after Na+ channels have already been opened (inactivated-state block).
authors: Department of Medicine, University of Chicago Pritzker School of Medicine, Illinois 60637.
authors: J A
authors: JA
authors: Wasserstrom
authors: J J
authors: JJ
authors: Salata
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D004347:Drug Interactions; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology*; D008839:Microelectrodes; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*; D016276:Ventricular Function
chemical_list: D007473:Ion Channels; D013779:Tetrodotoxin; D008012:Lidocaine; D012964:Sodium