Weinstein A M
Department of Physiology and Biophysics, Cornell University Medical College, New York, New York 10021.
Am J Physiol. 1994 Aug;267(2 Pt 2):F237-48. doi: 10.1152/ajprenal.1994.267.2.F237.
Pathways for ammonia transport have been incorporated within a model of rat proximal tubule [A. M. Weinstein. Am. J. Physiol. 263 (Renal Fluid Electrolyte Physiol. 32): F784-F798, 1992]. The luminal membrane includes a Na+/NH4+ exchanger, while at the peritubular membrane there is uptake of NH4+ on the Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase); both luminal and peritubular cell membranes contain conductive pathways for NH4+. The model equations have been expanded to include cellular ammoniagenesis. The principal focus of this study is the interplay of forces that can raise proximal tubule fluid total ammonia concentration 10-fold higher than in arterial plasma. Analysis of a cellular model reveals that luminal membrane Na+/NH4+ exchange, cellular production of ammonia, and peritubular membrane NH4+ uptake (via Na(+)-K(+)-ATPase or via K+ channel) all act in parallel to drive ammonia secretion. This derives from the cellular interconversion of NH4+ and NH3 and the free permeation of NH3 across cell membranes. It implies that inhibition of the luminal membrane transporter does not block the contribution of peritubular uptake to the overall active transport of ammonia. Conversely, when inhibition of the luminal membrane Na+/NH4+ entry (i.e., Na+/H+ inhibition) depresses transcellular Na+ flux, then the decrease of NH4+ flux through the peritubular Na+ pump enhances the apparent importance of the luminal membrane pathway. This analysis is confirmed in the numerical calculations and is a departure from the Ussing paradigm of series membrane Na+ transport. Although active secretion of ammonia by this tubule is substantial, the relative contribution of luminal Na+/NH4+ exchange and of peritubular uptake via the Na+ pump remains uncertain. The determination of peritubular capillary NH4+ concentration will be crucial to resolving this uncertainty, with lower concentration (i.e., closer to systemic arterial ammonia) obligating greater luminal membrane Na+/NH4+ exchange.
氨转运途径已被纳入大鼠近端小管模型中[A. M. 温斯坦。《美国生理学杂志》263卷（肾脏液体电解质生理学32）：F784 - F798，1992年]。管腔膜包含一个Na⁺/NH₄⁺交换体，而在肾小管周围膜上，NH₄⁺通过钠钾腺苷三磷酸酶（Na⁺ - K⁺ - ATP酶）被摄取；管腔和肾小管周围细胞膜都含有NH₄⁺的传导途径。模型方程已扩展到包括细胞氨生成。本研究的主要重点是那些能使近端小管液中总氨浓度比动脉血浆中高10倍的各种力量之间的相互作用。对一个细胞模型的分析表明，管腔膜Na⁺/NH₄⁺交换、细胞氨生成以及肾小管周围膜NH₄⁺摄取（通过Na⁺ - K⁺ - ATP酶或通过钾通道）都并行起作用以驱动氨分泌。这源于NH₄⁺和NH₃的细胞内相互转化以及NH₃跨细胞膜的自由通透。这意味着抑制管腔膜转运体并不会阻断肾小管周围摄取对氨整体主动转运的贡献。相反，当抑制管腔膜Na⁺/NH₄⁺进入（即抑制Na⁺/H⁺）降低跨细胞Na⁺通量时，那么通过肾小管周围钠泵的NH₄⁺通量的减少会增强管腔膜途径的表观重要性。这一分析在数值计算中得到证实，并且与串联膜Na⁺转运的乌斯辛范式不同。尽管该肾小管对氨的主动分泌量很大，但管腔Na⁺/NH₄⁺交换以及通过钠泵的肾小管周围摄取的相对贡献仍不确定。确定肾小管周围毛细血管NH₄⁺浓度对于解决这一不确定性至关重要，较低的浓度（即更接近全身动脉氨浓度）会使管腔膜Na⁺/NH₄⁺交换作用更大。
