Tetrahydroacridine inhibits voltage-dependent Na(+) current in guinea-pig ventricular myocytes
Abstract
AIM:
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.
CONCLUSION:
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.
Keywords:
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.
CONCLUSION:
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.