A difference in inward rectification and polyamine block and permeation between the Kir2.1 and Kir3.1/Kir3.4 K+ channels
A difference in inward rectification and polyamine block and permeation between the Kir2.1 and Kir3.1/Kir3.4 K+ channels
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DOI：
10.1113/jphysiol.2005.085746
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发表时间：
2005-11-01
影响因子：
5.5
通讯作者：
Boyett, MR
中科院分区：
文献类型：
--
作者：
Makary, SMY;Claydon, TW;Boyett, MR
内向整流是由细胞内Mg 2+和多胺如精胺对通道孔的电压依赖性阻断引起的。在本研究中，我们比较了心脏电流I-K，I-ACh的基础Kir3.1/Kir3.4通道和心脏电流I-K，I-1的基础Kir2.1通道的内向整流。在K+反转电位正的电位下，通过Kir3.1/Kir3.4观察到持续外向电流，而不是Kir2.1，这表明Kir3.1/Kir3.4比Kir2.1表现出更弱的向内整流。我们发现Kir3.1/Kir3.4比Kir2.1对细胞外精胺阻滞更敏感，并且细胞内和细胞外多胺可以在有限的程度上渗透Kir3.1/Kir3.4，但不能渗透Kir2.1。我们描述了一个简单的动力学模型，其中多胺作为渗透阻滞剂的Kir3.1/Kir3.4，但作为相对不渗透阻滞剂的Kir2.1。该模型显示了对细胞外精胺阻滞的敏感性的差异，以及两个通道之间向内整流程度的差异。这表明Kir3.1/Kir3.4表现出比Kir2.1更弱的内向整流，这是由于两个通道的多胺阻断和渗透平衡的差异。
Inward rectification is caused by voltage-dependent block of the channel pore by intracellular Mg2+ and polyamines such as spermine. In the present study, we compared inward rectification in the Kir3.1/Kir3.4 channel, which underlies the cardiac current I-K,I-ACh, and the Kir2.1 channel, which underlies the cardiac current I-K,I-1 - Sustained outward current at potentials positive to the K+ reversal potential was observed through Kir3.1/Kir3.4, but not Kir2.1, demonstrating that Kir3.1/Kir3.4 exhibits weaker inward rectification than Kir2.1. We show that Kir3.1/Kir3.4 is more sensitive to extracellular spermine block than Kir2.1, and that intracellular and extracellular polyamines can permeate Kir3.1/Kir3.4, but not Kir2.1, to a limited extent. We describe a simple kinetic model in which polyamines act as permeant blockers of Kir3.1/Kir3.4, but as relatively impermeant blockers of Kir2.1. The model shows the difference in sensitivity to extracellular spermine block, as well as the difference in the extent of inward rectification between the two channels. This suggests that Kir3.1/Kir3.4 exhibits weaker inward rectification than Kir2.1 because of the difference in the balance of polyamine block and permeation of the two channels.