生物谷報道：著名的華裔美國科學(xué)院院士伉儷詹裕農(nóng)和葉公杼剛剛在PNAS發(fā)表一篇文章稱,，傳統(tǒng)認(rèn)為K通道對離子的通透性是因為鉀子去水化，從而使離子合適K通道的孔徑,，從而獲得相對特異性的通透性的說法并不成立,。其選擇性通透性可能是其它機(jī)理。
他們采取了突變的Kir3.2通道,，將選擇性通透性的結(jié)合位點(diǎn)---一個酸性殘基放在通道孔中,，進(jìn)一步測量靜息離子通過量,。同時建立了個多離子通透模型以計算通道對K和Na離子通透的比例,。這些動力模型揭示了完全與傳統(tǒng)相反的觀點(diǎn)，似乎K離子通道對K離子的選擇通透性原理似乎與K離子去水化無關(guān),。
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.
原始出處：
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]
