Jacobson H R
J Clin Invest. 1984 Dec;74(6):2107-14. doi: 10.1172/JCI111635.
The medullary collecting duct (MCD) from renal outer medulla possesses significant HCO3 absorptive capacity. In vitro microperfusion studies have shown that HCO3 absorption in this segment is carbonic anhydrase dependent, affected by peritubular and luminal chloride concentrations, is independent of the presence of Na or the presence of Na transport, and is stimulated by mineralocorticoid hormone. The present in vitro microperfusion studies defined regulatory influences on MCD acidification as assessed by acute changes in the extracellular K and HCO3 concentrations and pCO2. These studies showed that acute changes in the peritubular K concentration to either 0 mM K or 50 mM K have no significant effect on HCO3 absorption in MCD. Intracellular voltage recordings showed that elevation of peritubular K concentration from 5 to 50 mM produced only a 2.8 mV depolarization of the basolateral cell membrane of MCD cells. In addition, acute reduction of peritubular K from 5 to 0 mM had no significant effect on intracellular voltage. Studies that were designed to assess the effects of HCO3 concentration and pCO2 on acidification showed that acute reduction of peritubular HCO3 concentration from 25 to 5 mM (pH change from 7.4 to 6.8) increased lumen-positive voltage from 30.2 +/- 3.8 to 40.0 +/- 4.4 mV, and simultaneously increased net HCO3 absorption from 15.6 +/- 1.9 to 22.9 +/- 2.9 pmol X mm-1 X min-1. Elevation of peritubular HCO3 concentration from 25 to 50 mM (pH change from 7.4 to 7.8) significantly decreased lumen-positive voltage from 33.8 +/- 2.4 to 26.7 +/- 1.5 mV and simultaneously decreased net HCO3 absorption from 17.9 +/- 1.2 to 12.8 +/- 1.3 pmol X mm-1 X min-1. In addition, acute reduction of peritubular pCO2 from 40 to less than 14 mmHg (final pH 7.8-7.9) significantly decreased lumen-positive voltage from 31 +/- 4.4 to 15.7 +/- 1.0 mV. Coincidentally, HCO3 absorption decreased significantly from 11.0 +/- 3.7 to 5.3 +/- 0.7 pmol X mm-1 X min-1. We conclude that: alteration of peritubular K concentration from 0 to 50 mM in vitro does not affect HCO3 absorption in the MCD, and that this lack of effect appears to be related to a low basolateral cell membrane K conductance; net HCO3 absorption and the associated lumen-positive voltage can be modulated by in vitro changes in peritubular HCO3 and pCO2 (or pH); and the MCD perfused in vitro appears to be a good model for studying the mechanisms and regulation of distal nephron acidification.
肾外髓质的髓质集合管(MCD)具有显著的HCO₃吸收能力。体外微灌注研究表明,该节段的HCO₃吸收依赖碳酸酐酶,受肾小管周围和管腔氯离子浓度影响,与Na的存在或Na转运无关,并受盐皮质激素刺激。目前的体外微灌注研究确定了对MCD酸化的调节影响,这是通过细胞外K和HCO₃浓度以及pCO₂的急性变化来评估的。这些研究表明,将肾小管周围K浓度急性改变为0 mM K或50 mM K对MCD中的HCO₃吸收没有显著影响。细胞内电压记录显示,肾小管周围K浓度从5 mM升高到50 mM仅使MCD细胞基底外侧细胞膜去极化2.8 mV。此外,肾小管周围K从5 mM急性降低到0 mM对细胞内电压没有显著影响。旨在评估HCO₃浓度和pCO₂对酸化影响的研究表明,将肾小管周围HCO₃浓度从25 mM急性降低到5 mM(pH从7.4变为6.8)可使管腔正电压从30.2±3.8 mV增加到40.0±4.4 mV,同时使净HCO₃吸收从15.6±1.9 pmol·mm⁻¹·min⁻¹增加到22.9±2.9 pmol·mm⁻¹·min⁻¹。将肾小管周围HCO₃浓度从25 mM升高到50 mM(pH从7.4变为7.8)可使管腔正电压从33.8±2.4 mV显著降低到26.7±1.5 mV,同时使净HCO₃吸收从17.9±1.2 pmol·mm⁻¹·min⁻¹降低到12.8±1.3 pmol·mm⁻¹·min⁻¹。此外,将肾小管周围pCO₂从40 mmHg急性降低到小于14 mmHg(最终pH 7.8 - 7.9)可使管腔正电压从31±4.4 mV显著降低到15.7±1.0 mV。同时,HCO₃吸收从11.0±3.7 pmol·mm⁻¹·min⁻¹显著降低到5.3±0.7 pmol·mm⁻¹·min⁻¹。我们得出结论:体外将肾小管周围K浓度从0改变到50 mM不会影响MCD中的HCO₃吸收,这种缺乏影响似乎与基底外侧细胞膜低K电导有关;净HCO₃吸收和相关的管腔正电压可通过体外肾小管周围HCO₃和pCO₂(或pH)的变化进行调节;体外灌注的MCD似乎是研究远端肾单位酸化机制和调节的良好模型。