抗心律失常药E-4031通过蛋白激酶C途径影响豚鼠心室肌细胞Na^+/Ca^(2+)交换(英文)  

Influence of antiarrhythmic agent E-4031 on Na^+/Ca^(2+) exchange by protein kinase C pathway in guinea pig ventricular myocytes

作　　者：武冬梅[1] 吕吉元[1] 吴博威[1] 

机构地区：[1]山西医科大学生理学教研室,山西太原030001

出　　处：《中国药理学与毒理学杂志》2000年第4期253-257,共5页Chinese Journal of Pharmacology and Toxicology

摘　　要：应用全细胞电压钳技术的斜坡脉冲程序 ,测定离体豚鼠心肌细胞准稳态电流 -电压关系曲线 ,研究E- 40 31增强 Na+ /Ca2 + 交换电流的机理 .结果表明蛋白激酶 C激动剂十四酰佛波乙酯 ( TPA) 5,1 0和1 5nmol· L-1使膜电位 + 50 m V时的 Ni2 +敏感电流分别增加 ( 1 1 6± 43) % ,( 2 2 5± 63) %和 ( 2 89±69) % .使膜电位 - 1 0 0 m V时的 Ni2 + 敏感电流分别增加 ( 2 9± 1 7) % ,( 1 0 4± 2 1 ) %和 ( 1 40± 2 9) % .蛋白激酶 C拮抗剂他莫昔芬 2 0 μmol· L-1可完全阻断 E- 40 31和 TPA对该电流的刺激作用 .结果提示 ,E- 40 31通过蛋白激酶 C途径激动 Na+ /Ca2 +交换 .To investigate the possible signaling pathways of E 4031 increasing Na +/Ca 2+ exchange, the quasi steady state current voltage relationship from the isolated guinea pig ventricular myocytes was measured using whole cell voltage clamp techniques with a ramp pulse protocol. The results showed that at potential of +50 mV, 12 O tetradecanoylphorbol 13 acetate (TPA), a protein kinase C activator, 5, 10, and 15 nmol·L -1 increased the Ni 2+ sensitive current by (116±43)%, (225±63)%, and (289±69)%, respectively. Tamoxifen, a selective antagonist of protein kinase C, 20 μmol·L -1 completely prevented the current changes induced by E 4031 and TPA. The results suggest that E 4031 stimulate the Na +/Ca 2+ exchange via a protein kinase C dependent pathway.

关 键 词：抗心律失常药 E-4031 蛋白激酶C 心肌 钠 钙 

分 类 号：R96[医药卫生—药理学]