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PNAS:钾离子通道的选择通透机制被华人科学家推翻

来源:本站原创 2006-10-05 22:52

相关报道: 夫妇相随--记华裔美国科学院院士伉俪詹裕农和叶公杼

   生物谷报道:著名的华裔美国科学院院士伉俪詹裕农和叶公杼刚刚在PNAS发表一篇文章称,传统认为K通道对离子的通透性是因为钾子去水化,从而使离子合适K通道的孔径,从而获得相对特异性的通透性的说法并不成立。其选择性通透性可能是其它机理。

  他们采取了突变的Kir3.2通道,将选择性通透性的结合位点---一个酸性残基放在通道孔中,进一步测量静息离子通过量。同时建立了个多离子通透模型以计算通道对K和Na离子通透的比例。这些动力模型揭示了完全与传统相反的观点,似乎K离子通道对K离子的选择通透性原理似乎与K离子去水化无关。

Potassium channels are necessary for a number of essential biological tasks such as the generation of action potentials and setting the resting membrane potential in cells, both of which require that these channels selectively permit the passage of potassium ions while suppressing the flow of other ions. Generally, this selectivity is attributed to a narrow stretch of the channel known as the selectivity filter. Over this stretch ions are dehydrated, and the backbone oxygen atoms of the protein mimic the ion's loss of coordination by water. However, channels are long pores with spatially distinct ion-binding sites that all must be traversed during ion permeation. We have shown that selectivity of mutant Kir3.2 (GIRK2) channels can be substantially amplified by introducing acidic residues into the cavity, a binding site below the selectivity filter. Here, we carry out electrostatic calculations on homology models to quantify the degree of stabilization that these mutations have on ions in the cavity. We then construct a multiion model of ion permeation to calculate the channel's permeability to potassium relative to sodium. This kinetic model uses rates derived from the electrostatic calculations and demonstrates that nonselective electrostatic stabilization of cations in the cavity can amplify channel selectivity independently of the selectivity filter. This nonintuitive result highlights the dependence of channel properties on the entire channel architecture and suggests that selectivity may not be fully understood by focusing solely on thermodynamic considerations of ion dehydration and the energetics of the selectivity filter.

原始出处:

Michael Grabe, Delphine Bichet, Xiang Qian, Yuh Nung Jan, and Lily Yeh Jan

K+ channel selectivity depends on kinetic as well as thermodynamic factors
PNAS 2006 103: 14361-14366; published online before print September 18 2006, 10.1073/pnas.0606662103 [Abstract] [Full Text] [Figures Only] [PDF] [Supporting Information]
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