Soleimani M, Bergman J A, Hosford M A, McKinney T D
Department of Medicine, Indiana University Medical Center, Indianapolis.
J Clin Invest. 1990 Oct;86(4):1076-83. doi: 10.1172/JCI114810.
Most HCO3- reabsorption in proximal tubules occurs via electroneutral Na+/H+ exchange in brush border membranes (BBMS) and electrogenic Na+:CO3=:HCO3- cotransport in basolateral membranes (BLMS). Since potassium depletion (KD) increases HCO3- reabsorption in proximal tubules, we evaluated these transport systems using BBM and BLM vesicles, respectively, from control (C) and KD rats. Feeding rats a potassium deficient diet for 3-4 wk resulted in lower plasma [K+] (2.94 mEq/liter, KD vs. 4.47 C), and higher arterial pH (7.51 KD vs. 7.39 C). KD rats gained less weight than C but had higher renal cortical weight. Influx of 1 mM 22Na+ at 5 s (pHo 7.5, pHi 6.0, 10% CO2, 90% N2) into BLM vesicles was 44% higher in the KD group compared to C with no difference in equilibrium uptake. The increment in Na+ influx in the KD group was DIDS sensitive, suggesting that Na+:CO3=:HCO3- cotransport accounted for the observed differences. Kinetic analysis of Na+ influx showed a Km of 8.2 mM in KD vs. 7.6 mM in C and Vmax of 278 nmol/min/mg protein in KD vs. 177 nmol/min/mg protein in C. Influx of 1 mM 22Na+ at 5 s (pHo 7.5, pHi 6.0) into BBM vesicles was 34% higher in the KD group compared to C with no difference in equilibrium uptake. The increment in Na+ influx in the KD group was amiloride sensitive, suggesting that Na+/H+ exchange was responsible for the observed differences. Kinetic analysis of Na+ influx showed a Km of 6.2 mM in KD vs. 7.1 mM in C and Vmax of 209 nmol/min/mg protein in KD vs. 144 nmol/min/mg protein in C. Uptakes of Na(+)-dependent [3H]glucose into BBM and [14C]succinate into BLM vesicles were not different in KD and C groups, suggesting that the Na+/H+ exchanger and Na+:CO3=:HCO3- cotransporter activities were specifically altered in KD. We conclude that adaptive increases in basolateral Na+:CO3=:HCO3- cotransport and luminal Na+H+ exchange are likely responsible for increased HCO3- reabsorption in proximal tubules of KD animals.
近端肾小管中大部分HCO₃⁻的重吸收是通过刷状缘膜(BBM)中的电中性Na⁺/H⁺交换以及基底外侧膜(BLM)中的电生性Na⁺:CO₃²⁻:HCO₃⁻共转运来实现的。由于低钾血症(KD)会增加近端肾小管中HCO₃⁻的重吸收,我们分别使用来自对照(C)和KD大鼠的BBM和BLM囊泡对这些转运系统进行了评估。给大鼠喂食低钾饮食3 - 4周会导致血浆[K⁺]降低(KD组为2.94 mEq/升,C组为4.47),动脉血pH升高(KD组为7.51,C组为7.39)。KD大鼠体重增加少于C组,但肾皮质重量更高。在5秒时(pHo 7.5,pHi 6.0,10% CO₂,90% N₂),1 mM ²²Na⁺流入BLM囊泡的量在KD组比C组高44%,平衡摄取量无差异。KD组Na⁺流入量的增加对DIDS敏感,表明Na⁺:CO₃²⁻:HCO₃⁻共转运是观察到的差异的原因。Na⁺流入的动力学分析显示,KD组的Km为8.2 mM,C组为7.6 mM,KD组的Vmax为278 nmol/min/mg蛋白,C组为177 nmol/min/mg蛋白。在5秒时(pHo 7.5,pHi 6.0),1 mM ²²Na⁺流入BBM囊泡的量在KD组比C组高34%,平衡摄取量无差异。KD组Na⁺流入量的增加对氨氯地平敏感,表明Na⁺/H⁺交换是观察到的差异的原因。Na⁺流入的动力学分析显示,KD组的Km为6.2 mM,C组为7.1 mM,KD组的Vmax为209 nmol/min/mg蛋白,C组为144 nmol/min/mg蛋白。KD组和C组中Na⁺依赖性[³H]葡萄糖进入BBM囊泡以及[¹⁴C]琥珀酸进入BLM囊泡的摄取量没有差异,这表明KD组中Na⁺/H⁺交换体和Na⁺:CO₃²⁻:HCO₃⁻共转运体的活性发生了特异性改变。我们得出结论,基底外侧Na⁺:CO₃²⁻:HCO₃⁻共转运和管腔Na⁺/H⁺交换的适应性增加可能是KD动物近端肾小管中HCO₃⁻重吸收增加的原因。