Balasubramanian S, Lynch J W, Barry P H
School of Physiology and Pharmacology, University of New South Wales, Sydney, Australia.
J Membr Biol. 1995 Jul;146(2):177-91. doi: 10.1007/BF00238007.
The permeation of monovalent organic cations through adenosine 3',5'-cyclic monophosphate-(cAMP) activated channels was studied by recording macroscopic currents in excised inside-out membrane patches from the dendritic knobs of isolated mammalian olfactory receptor neurons (ORNs). Current-voltage relations were measured when bathing solution Na+ was replaced by monovalent organic cations. Permeability ratios relative to Na+ ions were calculated from changes in reversal potentials. Some of the small organic cations tested included ammonium (NH4+), hydroxylammonium and formamidinium, with relative permeability ratios of 1.41, 2.3 and 1.01 respectively. The larger methylated and ethylated ammonium ions studied included: DMA (dimethylammonium), TMA (tetramethylammonium) and TEA (tetraethylammonium) and they all had permeability ratios larger than 0.09. Even large cations such as choline, arginine and tris(hydroxymethyl)aminomethane (Tris) were appreciably permeant through the cAMP-activated channel with permeability ratios ranging from 0.19 to 0.7. The size of the permeating cations, as assessed by molecular weight, was a good predictor of the permeability. The permeability sequence of the cAMP-activated channel in our study was PNH4 > PNa > PDMA > PTMA > PCholine > PTEA. Higher permeability ratios of hydroxylammonium, arginine and tris(hydroxymethyl)aminomethane cannot be explained by ionic size alone. Our results indicate that: (i) cAMP-activated channels poorly select between monovalent cations; (ii) the pore dimension must be at least 6.5 x 6.5 A, in order to allow TEA and Tris to permeate and (iii) molecular sieving must be an important mechanism for the permeation of large organic ions through the channels with specific ion binding playing a smaller role than in other structurally similar channels. In addition, the results clearly indicate that cyclic nucleotide-gated (CNG) channels in different cells are not the same, the olfactory CNG channel being different from that of the photoreceptors, particularly with respect to the permeation of large organic cations, which the ORN channels allow to permeate readily.
通过记录从分离的哺乳动物嗅觉受体神经元（ORN）树突棘上切除的内向外膜片的宏观电流，研究了单价有机阳离子通过3',5'-环磷酸腺苷（cAMP）激活通道的渗透情况。当用单价有机阳离子替代浴液中的Na+时，测量电流-电压关系。根据反转电位的变化计算相对于Na+离子的渗透率。测试的一些小有机阳离子包括铵离子（NH4+）、羟铵离子和甲脒离子，其相对渗透率分别为1.41、2.3和1.01。研究的较大的甲基化和乙基化铵离子包括：二甲铵（DMA）、四甲铵（TMA）和四乙铵（TEA），它们的渗透率均大于0.09。甚至像胆碱、精氨酸和三（羟甲基）氨基甲烷（Tris）这样的大阳离子也能明显地通过cAMP激活通道，渗透率在0.19至0.7之间。通过分子量评估的渗透阳离子大小是渗透率的良好预测指标。在我们的研究中，cAMP激活通道的渗透率顺序为PNH4 > PNa > PDMA > PTMA > P胆碱 > PTEA。羟铵离子、精氨酸和三（羟甲基）氨基甲烷较高的渗透率不能仅用离子大小来解释。我们的结果表明：（i）cAMP激活通道对单价阳离子的选择性较差；（ii）孔尺寸必须至少为6.5×6.5 Å，以便允许TEA和Tris渗透；（iii）分子筛分必定是大有机离子通过通道渗透的重要机制，与其他结构相似的通道相比，特定离子结合所起的作用较小。此外，结果清楚地表明不同细胞中的环核苷酸门控（CNG）通道并不相同，嗅觉CNG通道与光感受器的不同，特别是在大有机阳离子的渗透方面，ORN通道能够轻易允许其渗透。
