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  • Title: Tetrahydroacridine inhibits voltage-dependent Na(+) current in guinea-pig ventricular myocytes.
    Author: Wang W, Wang YP, Hu GY.
    Journal: Acta Pharmacol Sin; 2004 Sep; 25(9):1138-44. PubMed ID: 15339388.
    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.
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