Sugiharto Silas, Lewis Trevor M, Moorhouse Andrew J, Schofield Peter R, Barry Peter H
Department of Physiology and Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
Biophys J. 2008 Nov 15;95(10):4698-715. doi: 10.1529/biophysj.107.125690. Epub 2008 Aug 15.
The functional role of ligand-gated ion channels depends critically on whether they are predominantly permeable to cations or anions. However, these, and other ion channels, are not perfectly selective, allowing some counterions to also permeate. To address the mechanisms by which such counterion permeation occurs, we measured the anion-cation permeabilities of different alkali cations, Li(+) Na(+), and Cs(+), relative to either Cl(-) or NO(3)(-) anions in both a wild-type glycine receptor channel (GlyR) and a mutant GlyR with a wider pore diameter. We hypothesized and showed that counterion permeation in anionic channels correlated inversely with an equivalent or effective hydrated size of the cation relative to the channel pore radius, with larger counterion permeabilities being observed in the wider pore channel. We also showed that the anion component of conductance was independent of the nature of the cation. We suggest that anions and counterion cations can permeate through the pore as neutral ion pairs, to allow the cations to overcome the large energy barriers resulting from the positively charged selectivity filter in small GlyR channels, with the permeability of such ion pairs being dependent on the effective hydrated diameter of the ion pair relative to the pore diameter.
配体门控离子通道的功能作用关键取决于它们主要对阳离子还是阴离子具有通透性。然而，这些以及其他离子通道并非具有完美的选择性，会允许一些反离子也通过。为了探究这种反离子通透发生的机制，我们测量了野生型甘氨酸受体通道（GlyR）和孔径更大的突变型GlyR中不同碱金属阳离子Li⁺、Na⁺和Cs⁺相对于Cl⁻或NO₃⁻阴离子的阴离子-阳离子通透性。我们假设并证明，阴离子通道中的反离子通透与阳离子相对于通道孔径半径的等效或有效水合尺寸呈负相关，在孔径更大的通道中观察到更大的反离子通透性。我们还表明，电导的阴离子成分与阳离子的性质无关。我们认为，阴离子和反离子阳离子可以作为中性离子对通过孔道，以使阳离子能够克服小GlyR通道中带正电的选择性过滤器所产生的巨大能量屏障，这种离子对的通透性取决于离子对相对于孔径的有效水合直径。
