Unique Kir2.x properties determine regional and species differences in the cardiac inward rectifier K+ current
Unique Kir2.x properties determine regional and species differences in the cardiac inward rectifier K+ current
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DOI：
10.1161/01.res.0000128408.66946.67
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发表时间：
2004-05-28
影响因子：
20.1
通讯作者：
Anumonwo, JMB
中科院分区：
文献类型：
--
作者：
Dhamoon, AS;Pandit, SV;Anumonwo, JMB
内向整流钾(KIR)2.x通道介导心脏内向整流钾电流(I-K1)。除了电流密度的差异外，心房和心室I-K1在外向电流分布和细胞外钾([K+](O))依赖性上也存在差异。用全细胞膜片钳技术研究了豚鼠和绵羊心脏异源表达的Kir2.x通道以及心房和心室I-K1的上述特性。Kir2.x通道显示出明显的整流曲线：Kir2.1和Kir2.2在去极化大于-30 mV(I约为0pA)的情况下完全整流。相比之下，Kir2.3渠道的整改工作没有完成。在主要表达Kir2.1的豚鼠心房中，I-K1被完全纠正。在以Kir2.3通道为主的绵羊心房中，I-K1不能完全整流。绵羊Kir2.3通道的单通道分析显示，15个细胞的平均单位电导为13.1+/-0.1pS，这与绵羊心房的I-K1相对应(32个细胞为9.9+/-0.1pS)。外向Kir2.1电流在10 mmoL/L[K+](O)时增加，而Kir2.3电流不增加。相应地，豚鼠(而不是绵羊)心房I-K1在10 mmol/L[K+](O)时表现出外向电流的增加。尽管两种动物的脑室都表达Kir2.1和Kir2.3，但外向I-K1电流完全整流并在高[K+](O)时增加，表现出Kir2.1样特性。同样，异源表达的Kir2.1-Kir2.3络合物在正常和10 mmol/L[K+](O)中的外向电流特性与Kir2.1相似，但与Kir2.3不同。因此，单个Kir2.x亚型以及异构体Kir2.x复合体的独特性质决定了I-K1在心脏中的区域和物种差异。
The inwardly rectifying potassium (Kir) 2.x channels mediate the cardiac inward rectifier potassium current (I-K1). In addition to differences in current density, atrial and ventricular I-K1 have differences in outward current profiles and in extracellular potassium ([K+](o)) dependence. The whole-cell patch-clamp technique was used to study these properties in heterologously expressed Kir2.x channels and atrial and ventricular I-K1 in guinea pig and sheep hearts. Kir2.x channels showed distinct rectification profiles: Kir2.1 and Kir2.2 rectified completely at potentials more depolarized than -30 mV (Iapproximate to0 pA). In contrast, rectification was incomplete for Kir2.3 channels. In guinea pig atria, which expressed mainly Kir2.1, I-K1 rectified completely. In sheep atria, which predominantly expressed Kir2.3 channels, I-K1 did not rectify completely. Single-channel analysis of sheep Kir2.3 channels showed a mean unitary conductance of 13.1 +/- 0.1 pS in 15 cells, which corresponded with I-K1 in sheep atria (9.9 +/- 0.1 pS in 32 cells). Outward Kir2.1 currents were increased in 10 mmol/L [K+](o), whereas Kir2.3 currents did not increase. Correspondingly, guinea pig ( but not sheep) atrial I-K1 showed an increase in outward currents in 10 mmol/L [K+](o). Although the ventricles of both species expressed Kir2.1 and Kir2.3, outward I-K1 currents rectified completely and increased in high [K+](o)-displaying Kir2.1-like properties. Likewise, outward current properties of heterologously expressed Kir2.1-Kir2.3 complexes in normal and 10 mmol/L [K+](o) were similar to Kir2.1 but not Kir2.3. Thus, unique properties of individual Kir2.x isoforms, as well as heteromeric Kir2.x complexes, determine regional and species differences of I-K1 in the heart.