Tetrahydroacridine inhibits voltage-dependent Na^+ current in guinea-pig ventricular myocytes  

作　　者：WeiWANG Yi-pingWANG Guo-yuanHU 

机构地区：[1]StateKeyLaboratoryofDrugResearch,ShanghaiInstituteofMateriaMedica,ShanghaiInstitutesforBiologicalSciences,ChineseAcademyofSciences,Shanghai201203,China [2]TheFirstDepartmentofPharmacology,ShanghaiInstituteofMateriaMedica,ShanghaiInstitutesforBiologicalSciences,ChineseAcademyofSciences,Shanghai201203,China

出　　处：《Acta Pharmacologica Sinica》2004年第9期1138-1144,共7页中国药理学报（英文版）

基　　金：ProjectsupportedbyagrantfromtheNationalNaturalScienceFoundationofChina(30123005)

摘　　要：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 IC50 value of 120 umol/L (95 % confidence range: 108-133 umol/L). (2) The inhibitory effects of tacrine on Na+current exhibited both a tonic nature and use-dependence. (3) Tacrine at 100 umol/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.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 IC50 value of 120 umol/L (95 % confidence range: 108-133 umol/L). (2) The inhibitory effects of tacrine on Na+current exhibited both a tonic nature and use-dependence. (3) Tacrine at 100 umol/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.

关 键 词：Alzheimer disease cholinesterase inhibitors sodium channels tetrahydroacridine (tacrine) MYOCARDIUM patch-clamp techniques 

分 类 号：R749.16[医药卫生—神经病学与精神病学]