内向整流钾通道激动剂对大鼠异丙肾诱发心律失常的抑制作用  

Inhibitory effect of agonist of I_(K1) channel on arrhythmia induced by isoproterenol in rats

作　　者：李超红[1] 陈依春 翟旭雯[1] 封启龙[1] 

机构地区：[1]山西医科大学生理学系细胞生理学省部共建教育部重点实验室,山西太原030001

出　　处：《中国药理学通报》2015年第8期1081-1085,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30900492);山西省青年科学基金资助项目(No 2009021043-1);山西省高校"131"领军人才工程项目;山西省高等学校优秀青年学术带头人支持项目

摘　　要：目的观察内向整流钾通道(IK1通道)激动剂扎考必利(zacopride,Zac)对异丙肾上腺素(isoproterenol,ISO)诱发大鼠心律失常的抑制作用及其机制。方法 1利用麻醉状态大鼠体表心电图观察Zac对ISO诱发心律失常的效应;2利用细胞内微电极技术观察Zac对大鼠右心室乳头肌细胞静息电位及ISO联合高钙诱发延迟后除极(DADs)和触发活动(TA)的效应。结果 1 ISO组大鼠出现频发室性期前收缩及ST段下移;与之相比,ISO+Zac组大鼠室性期前收缩的发生率从100%降至50%(n=6,P<0.05),1 h内室性期前收缩的个数从1 574±521降至33±40(n=6,P<0.05)。2 Zac(1μmol·L-1)使正常大鼠右心室乳头肌细胞静息电位从(-74.42±1.95)m V增加至(-78.50±2.07)m V(n=6,P<0.05)。3 Zac(1μmol·L-1)可明显抑制ISO联合高钙诱发的大鼠右心室乳头肌DADs和TA,使其发生率从93.75%降至25%(n=16,P<0.05),且这一作用可被1μmol·L-1Ba Cl2反转。结论选择性IK1通道激动剂扎考必利可明显抑制ISO诱发的室性心律失常,其机制与它增强IK1,使膜电位负值增大和抑制延迟后除极有关。这一结果进一步支持适度增强IK1是一条可行的抗心律失常途径。Aim To investigate the inhibitory effects of zaeopride （Zac） on arrhythmia induced by isoproterenol （ISO） and the underlying mechanisms in rats. Meth- ods ①ECGs were recorded in anesthetized rats in vi- vo to observe the effects of zacopride on arrhythmia in- duced by ISO. ② Intraeellular microeleetrode tech- nique was used to investigate the effects of zaeopride on resting membrane potential, delayed afterdepolariza- tions （DADs） and triggered activity （TA） induced by ISO combined with 3.6 mmol · L-1 CaCl2 in right ven- tricular papillary muscle of rats. Results ①In ISO group rats, ventricular premature beats （ VPB ） oc- curred frequently with ST-segment depression. Com- pared with ISO group, the incidence of VPB in ISO ＋Zac group decreased from 100% to 50% （n = 6, P 〈0. 05 ） and the total number of VPB recorded in 1 hour significantly reduced from 1 574 ± 521 to 33± 40 （n = 6, P 〈 0. 05 ）. ② Zacopride at 1 μmol · L-1 could by-perpolarize the resting membrane potential of right ven- tricular papillary muscle in normal rat from （ - 74.42 ±1.95）mV to （ -78.50±2.07）mV （n=6, P〈 0. 05）. ③ Zacopride at 1 p, mol · L- 1 significantly de- pressed the DADs and TA induced by ISO combined with 3.6 mmol·L-1 CaC12 in right ventricular papilla- ry muscle. The incidence of DADs decreased from 93.75% in rats in ISO group to 25% in ISO ＋Zac group （ n = 16, P 〈 0. 05 ）, and this antiarrhythmic effect could be reversed by 1 μ mol·L-1 BaCl2.Conclusions Zacopride, a selective channel ago- nist, can significantly inhibit cardiac arrthymia induced by ISO in rats, the mechanism of which is mainly at- tributed to zacopride-induced hyperpolarization of the resting membrane potential and subsequent suppression of DADs and TA via enhancing IK1. These results pro-vide further evidence that to enhance IL1 moderately may be a feasible pathway for antiarrthymic therapy.

关 键 词：内向整流钾通道 扎考必利 静息电位 延迟后除极 触发活动 异丙肾上腺素 心律失常 

分 类 号：R-332[医药卫生] R329.24