title: Tetrahydroacridine inhibits voltage-dependent Na(+) current in guinea-pig ventricular myocytes.
abstract: OBJECTIVE
  To study the effects of tetrahydroacridine (tacrine) on voltage-gated Na(+) channels in cardiac tissues.
  
  
  METHODS
  Single ventricular myocytes were enzymatically dissociated from adult guinea-pig heart. Voltage-dependent Na(+) current was recorded using whole cell voltage-clamp technique.
  
  
  RESULTS
  (1) Tacrine reversibly inhibited Na(+) current with an IC(50) value of 120 micromol/L (95 % confidence range: 108-133 micromol/L). (2) The inhibitory effects of tacrine on Na(+) current exhibited both a tonic nature and use-dependence. (3) Tacrine at 100 micromol/L caused a negative shift (about 10 mV) in the voltage-dependence of steady-state inactivation of Na(+) current, and retarded its recovery from inactivation, but did not affect its activation curve. (4) Intracellular application of tacrine significantly inhibited Na(+) current.
  
  
  CONCLUSIONS
  In addition to blocking other voltage-gated ion channels, tacrine blocked Na(+) channels in guinea-pig ventricular myocytes. Tacrine acted as inactivation stabilizer of Na(+) channels in cardiac tissues.
authors.affiliation: State Key Laboratory of Drug Research, The First Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Hu
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000187:drug effects*; D013619:Tacrine / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D015222:Sodium Channels; D013619:Tacrine