钙离子激活性氯通道在犬心力衰竭心肌功能重塑的观察  

Observation of functional remodeling of Ca^(2+) -activated CI^- channel in pacing-induced canine failing heart

作　　者：浦介麟[1] 李宁[1] 马克娟[1] 王洪涛[1] 腾思勇[1] Jonathon C.Makielski 

机构地区：[1]中国医学科学院中国协和医科大学阜外心血管病医院心律失常诊治中心,北京100037 [2]美国威斯康星大学医学院心脏科

出　　处：《中华心血管病杂志》2006年第9期797-800,共4页Chinese Journal of Cardiology

摘　　要：目的观察 I_(to)第2个成分 I_(to2)即钙离子激活性氯通道(CLCA)是否参与心力衰竭(心衰)心脏的功能重塑。方法快速起搏犬右心室,诱发心衰,酶学法分离心肌细胞,以经典膜片钳全细胞记录法评价心衰时 I_(to2)电流密度的变化、I_(to2)与 L-型钙通道电流(I_(Ca-L))的关系和在恒定的细胞内钙浓度条件下 I_(to2)与膜电压的关系。用氯通道阻断剂4,4′diisothiocyanostilbene-2,2′-disulfonic acid(DIDS)200μmol 筛选出 I_(to2)。结果 I_(to2)电压-电流关系呈倒钟型,与 I_(Ca-L)的曲线成镜影关系但右移10 mV_oI_(Ca-L)密度在心衰和对照组之间差异无统计学意义。在膜电压0～40 mV 之间,I_(to2)密度在心衰组明显减小。例如膜电压为20 mV 时,对照组与心衰组 I_(to2)分别为(3.02±0.55)pA/pF(n=7)和(1.31±0.25)pA/pF(n=8),P<0.05。I_(to2)电流的衰退时间常数在两组间差异无统计学意义。当细胞内钙浓度锁定在100μmol 时,I_(to2)密度在心衰组反而比对照组增大,提示 CLCA 功能上调。结论心衰时 I_(to2)密度下降,这可能与心衰细胞兴奋释放钙浓度下降有关。I(to2)密度下降可能参与心衰时的动作电位时程延长和晚期后除极的发生,可能是心衰时心律失常的发生机制之一。Objective To study whether Ca^2＋ -activated Cl^- current （Ito2） contributes to the functional remodeling of the failing heart. Methods The cardiac myocytes were isolated enzymatically from rapidly pacing-induced failing canine hearts （HF） at room temperature. Patch-Clamp whole cell recording technique was employed to record the Ito2. The Cl^- transport blocker 4,4＇-diisothiocyanosfilbene-2,2＇- disulfonic acid （DIDS, 200 μmol） was used to isolated the Ito2. The relations of In to L-type Ca^2＋ current （ ICa-L ） and to the membrane voltage under the constant intracellular [ Ca^2 ＋ ] i were evaluated in HF and the normal hearts. Results We found that the current density of In was significantly decreased in HF cells compared with the controls. At membrane voltage of 20 mV, for example, the In density was （3.02 ＋- 0. 54 ） pA/pF in control cells （ n = 7） vs. （ 1.31 ＋- 0. 25 ） pA/pF in HF （ n = 8） cells, P 〈 0. 05. While the averaged ICa-L density did not show difference between two groups. The time constant of current decay of In was similar in beth types of cells. However, in intracellular Ca^2＋ clamped mode with 100 μmol [ Ca^2＋ ] i, In density was increased significantly in HF cells at membrane voltage of ＋ 30 mV or higher. Conclusions Our results suggest that the decrease of In density may contribute to the prolongation of the action potential in failing heart. In density abnormality may cause cardiac arrhythmia and a delayed after-depolarization. Impaired Ca^2 ＋ handing in HF cells rather than reduced CLCA function itself may result in this abnormality.

关 键 词：心力衰竭 充血性 心律失常 氯化物通道 

分 类 号：R541.6[医药卫生—心血管疾病]