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+/Ca2+交换

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-4031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）5，10和15 nmol·L^-1使膜电位+50 mV时的Ni²⁺敏感电流分别增加（116±43）%，（225±63）% 和（289±69）%. 使膜电位-100 mV时的Ni²⁺敏感电流分别增加（29±17）%，（104±21）%和（140±29）%. 蛋白激酶C拮抗剂他莫昔芬20 μmol·L^-1可完全阻断E- 4031和TPA对该电流的刺激作用. 结果提示，E-4031通过蛋白激酶C途径激动Na⁺/Ca²⁺交换.

Influence of antiarrhythmic agent E-4031 on Na+/Ca2+ exchange by protein kinase C pathway in guinea pig ventricular myocytes

To investigate the possible signaling pathways of E-4031 increasing Na⁺/Ca²⁺ 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 Ni²⁺-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⁺/Ca²⁺ exchange via a protein kinase C- dependent pathway.