Tetrahydroacridine inhibits voltage-dependent Na(+) current in guinea-pig ventricular myocytes.
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.
Wang
Wei
W
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.
Wang
Yi-Ping
YP
Hu
Guo-Yuan
GY
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*
D002800:Cholinesterase Inhibitors; D015222:Sodium Channels; D013619:Tacrine