Active and passive components of chloride transport in the rat proximal convoluted tubule.

Rat proximal convoluted tubules were perfused in vivo to examine the active and passive components of chloride absorption. Chloride flux was a linear function of the transepithelial electrochemical driving force, yielding a permeability coefficient of 20.6 X 10(-5) cm/s. In the absence of an electrochemical driving force, chloride absorption persisted at the rate of 131 peq/mm X min, thus demonstrating active absorption of chloride. Addition of luminal cyanide to tubules absorbing chloride inhibited net chloride absorption. In tubules perfused with a low luminal chloride concentration in which there was net chloride secretion, addition of luminal cyanide increased the magnitude of net chloride secretion. These studies demonstrate that transepithelial chloride transport involves two components: a passive paracellular flux and an active transcellular flux. Cyanide affects net chloride flux by inhibiting active transcellular chloride absorption.     

Axial heterogeneity of intracellular pH in rat proximal convoluted tubule.

In the proximal convoluted tubule (PT), the HCO3- reabsorptive rate is higher in early (EPS) compared with late proximal segments (LPS). To examine the mechanism of this HCO3- reabsorption profile, intracellular pH (pHi) was measured along the superficial PT of the rat under free-flow and stationary microperfusion using the pH-sensitive fluorescence of 4-methylumbelliferone (4MU). With 4MU superfusion, pHi was found to decline along the PT. Observation with 365-nm excitation revealed that EPS were brightly fluorescent and always emerged away from their star vessel. Midproximal segments were darker and closer to the star vessel which was surrounded by the darkest LPS. Decreasing luminal HCO3- from 15 to 0 mM lowered pHi in both EPS and LPS, but pHi remained more alkaline in EPS with both perfusates. Thus the axial decline in pHi along the PT is due to both luminal factors and intrinsic differences in luminal H+ extrusion in PT cells.     

Calcium transport in the rabbit superficial proximal convoluted tubule.

Calcium transport was studied in isolated S2 segments of rabbit superficial proximal convoluted tubules. 45Ca was added to the perfusate for measurement of lumen-to-bath flux (JlbCa), to the bath for bath-to-lumen flux (JblCa), and to both perfusate and bath for net flux (JnetCa). In these studies, the perfusate consisted of an equilibrium solution that was designed to minimize water flux or electrochemical potential differences (PD). Under these conditions, JlbCa (9.1 +/- 1.0 peq/mm X min) was not different from JblCa (7.3 +/- 1.3 peq/mm X min), and JnetCa was not different from zero, which suggests that calcium transport in the superficial proximal convoluted tubule is due primarily to passive transport. The efflux coefficient was 9.5 +/- 1.2 X 10(-5) cm/s, which was not significantly different from the influx coefficient, 7.0 +/- 1.3 X 10(-5) cm/s. When the PD was made positive or negative with use of different perfusates, net calcium absorption or secretion was demonstrated, respectively, which supports a major role for passive transport. These results indicate that in the superficial proximal convoluted tubule of the rabbit, passive driving forces are the major determinants of calcium transport.     

Ammonia transport by early and late proximal convoluted tubule of the rat.

Free-flow micropuncture experiments were performed to examine ammonia transport separately in early and late proximal convoluted tubule (PCT) of the rat. In control rats, ammonia was secreted along the early PCT but was reabsorbed along the late PCT. In rats with chronic metabolic acidosis, ammonia secretion along the early PCT was increased compared with controls, and ammonia absorption by the late PCT was converted to small net ammonia secretion. In the acidotic rats, ammonia secretion rate in the early PCT was six times higher than that in the late PCT. Thus, most or all of ammonia secretion by the PCT occurred along its early portion. In control and acidotic rats, luminal NH3 concentration in the early PCT was significantly higher than that in the late PCT, indicating that ammonia is not in diffusion equilibrium throughout the renal cortex. It is proposed that differences in ammonia transport rate in early vs. late PCT may be due to differences in ammonia production rate and/or to differences in the rate of an ammonia backflux that detracts from net ammonia secretion.     

Neonatal rabbit juxtamedullary proximal convoluted tubule acidification.

The present in vitro microperfusion study examined apical membrane Na+/H+ antiporter and basolateral membrane Na(HCO3)3 symporter activity in newborn and adult juxtamedullary proximal convoluted tubules. Proton fluxes were determined from the initial rate of change of intracellular pH after a change in the luminal or bathing solution, buffer capacity, and tubular volume of newborn and adult tubules. Intracellular pH (pHi) was measured fluorometrically using the pH-sensitive dye (2',7')-bis (carboxyethyl)-(5,6)-carboxyfluorescein (BCECF). Apical Na+/H+ antiporter proton flux, assayed by the effect of sodium removal (147----0 meq/liter) on pHi, was one-third the adult level for the first 2 wk and doubled in the 3rd wk of life. Adult levels were achieved by 6 wk of age. Na+/H+ antiporter activity was not detected on the basolateral membrane of 1-wk-old newborns, indicating that polarity of this transporter was already present. Basolateral membrane Na(HCO3)3 proton flux, assayed by the effect of a bath bicarbonate change (25----5 meq/liter) and by a bath sodium change (147----0 meq/liter) on pHi, was 50-60% of adult values in 1-wk-old newborns. Basolateral membrane Na(HCO3)3 proton flux assayed by a bath bicarbonate change (25----5 meq/liter) remained at 50-60% of adult values for the 1st mo of life and increased to adult levels by 6 wk of age. This transporter not only plays a role in net acidification, but is an important determinant of cell pH in newborn juxtamedullary proximal convoluted tubules.     

Glucocorticoids stimulate rabbit proximal convoluted tubule acidification.

Glucocorticoids have an important role in renal acidification; however, a direct effect of glucocorticoids on proximal convoluted tubule (PCT) acidification has not been directly demonstrated. In the present in vitro microperfusion study PCT from animals receiving dexamethasone (600 micrograms/kg twice daily for 2 d and 2 h before killing) had a significantly higher rate of bicarbonate absorption than did controls (92.0 +/- 13.3 vs 59.9 +/- 3.2 pmol/mm.min, P < 0.01). To examine if glucocorticoids had a direct epithelial action, dexamethasone was added to the bath of PCT perfused in vitro. After 3 h of incubation in paired experiments 10(-6) M and 10(-5) M dexamethasone resulted in an approximately 30% stimulation in the rate of bicarbonate absorption. 10(-7) M dexamethasone and 10(-6) M aldosterone had no effect on bicarbonate absorption. The stimulation of acidification by 10(-5) M dexamethasone was blocked by actinomycin D and cycloheximide. These data are consistent with a direct effect of glucocorticoids on PCT acidification, and this effect is dependent upon protein synthesis.     

Intrinsic differences in various segments of the proximal convoluted tubule.

Until recently it has not been possible to compare directly the function of superficial and juxtamedullary nephrons. The present studies, using in vitro microperfusion, were designed to examine whether functional differences exist between proximal convoluted tubule segments of superficial and juxtamedullary nephrons. Electrophysiological studies showed that major differences exist between the relative chloride and sodium permeabilities of these segments. In the 1st mm of the superficial proximal convoluted tubule, the permeability to sodium was greater than that to chloride, whereas in the 2nd mm of the superficial proximal convoluted tubule and all later segments, the permeability to chloride was greater than that to sodium. The juxtamedullary proximal convoluted tubule was found to differ from the superficial proximal convoluted tubule in two respects: first, the relative permeabilities to chloride and sodium did not differ in the various segments of the juxtamedullary proximal convoluted tubule; second, the permeability to sodium was greater than to chloride throughout. When perfused with a solution lacking glucose and amino acids, the superficial and juxtamedullary convolutions exhibited the same transepithelial potential change, a reversible decrease to less than -- 1 mV. It thus appears that in both convolutions there exists electrogenic sodium transport coupled to the transport of these organic solutes. This differs from pars recta of both of these nephrons, which have been shown to exhibit electrogenic sodium transport independent of organic solutes. However, when perfused with a solution lacking glucose and amino acids but also containing high chloride and low bicarbonate concentrations, the superficial convolution developed a significantly more positive potential than the juxtamedullary. This difference reflects greater relative chloride permeability in the superficial proximal convolution. These studies show that intrinsic functional differences exist between proximal convoluted tubules obtained from the superficial and juxtamedullary nephron populations.     

Insulin stimulates volume absorption in the rabbit proximal convoluted tubule.

The present in vitro microperfusion study examined whether insulin affects volume absorption (Jv) in the proximal convoluted tubule (PCT). PCT were perfused with an ultrafiltrate-like solution and were bathed in a serum-like albumin solution. Addition of a physiologic concentration of 10(-10) M insulin to the bathing solution resulted in a stimulation of Jv and a more negative transepithelial potential difference (PD). There was a progressive stimulation of the lumen negative PD and Jv with higher insulin concentrations. Maximal stimulation occurred at 10(-8) M bath insulin. The insulin-induced stimulation of volume reabsorption was also observed when glucose and amino acids were removed from the luminal perfusate. Direct examination of the effect of insulin on glucose, chloride, and bicarbonate absorption demonstrated that the transport of all these solutes was stimulated by insulin. Addition of insulin to the luminal perfusate had no affect on Jv. These data show that insulin has a direct effect to stimulate Jv in the proximal tubule.     

Mechanism of NaCl and water reabsorption in the proximal convoluted tubule of rat kidney.

The role of chloride concentration gradients in proximal NaCl and water reabsorption was examined in superficial proximal tubules of the rat by using perfusion and collection techniques. Reabsorptive rates (Jv), chloride concentrations, and transtubular potential difference were measured during perfusion with solutions (A) simulating an ultrafiltrate of plasma; (B) similar to (A) except that 20 meq/liter bicarbonate was replaced with acetate; (C) resembling late proximal fluid (glucose, amino acid, acetate-free, low bicarbonate, and high chloride); and (D) in which glucose and amino acids were replaced with raffinose and bicarbonate was partially replaced by poorly reabsorbable anions (cyclamate,sulfate, and methyl sulfate). In tubules perfused with solutions A and B, Jv were 2.17 and 2.7 nl mm-1 min-1 and chloride concentrations were 131.5 +/- 3.1 and 135 +/- 395 meq/liter, respectively, indicating that reabsorption is qualitatively similar to free-flow conditions and that acetate adequately replaces bicarbonate. With solution C, Jv was 2.10 nl mm-1 min-1 and potential difference was +1.5 +/- 0.2 mV, indicating that the combined presence of glucose, alanine, acetate, and bicarbonate per se is not an absolute requirement. Fluid reabsorption was virtually abolished when tubules were perfused with D solutions; Jv was not significantly different from zero despite sodium and chloride concentrations similar to plasma; chloride concentration was 110.8 +/- 0.2 meq/liter and potential difference was -0.98 mV indicating that chloride was close to electrochemical equilibrium. These results suggest the importance of the chloride gradient to proximal tubule reabsorption in regions where actively reabsorbable solutes (glucose, alanine, acetate, and bicarbonate) are lacking and provide further evidence for a passive model of NaCl and water transport.     

Interaction of chloride and bicarbonate transport across the basolateral membrane of rabbit proximal straight tubule. Evidence for sodium coupled chloride/bicarbonate exchange.

The existence of chloride/bicarbonate exchange across the basolateral membrane and its physiologic significance were examined in rabbit proximal tubules. S2 segments of the proximal straight tubule were perfused in vitro and changes in intracellular pH (pHi) and chloride activity (aCli) were monitored by double-barreled microelectrodes. Total peritubular chloride replacement with gluconate increased pHi by 0.8, and this change was inhibited by a pretreatment with an anion transport inhibitor, SITS. Peritubular bicarbonate reduction increased aCli, and most of this increase was lost when ambient sodium was totally removed. The reduction rates of pHi induced by a peritubular bicarbonate reduction or sodium removal were attenuated by 20% by withdrawal of ambient chloride. SITS application to the bath in the control condition quickly increased pHi, but did not change aCli. However, the aCli slightly decreased in response to SITS when the basolateral bicarbonate efflux was increased by reducing peritubular bicarbonate concentration. It is concluded that sodium coupled chloride/bicarbonate exchange is present in parallel with sodium-bicarbonate cotransport in the basolateral membrane of the rabbit proximal tubule, and it contributes to the basolateral bicarbonate and chloride transport.     

Angiotensin II: a potent regulator of acidification in the rat early proximal convoluted tubule.

The early proximal convoluted tubule (PCT) is the site of 50% of bicarbonate reabsorption in the nephron, but its control by angiotensin II has not been previously studied. In vivo microperfusion was used in both the early and late PCT in Munich-Wistar rats. Systemic angiotensin II administration (20 ng/kg X min) or inhibition of endogenous angiotensin II activity with saralasin (1 microgram/kg X min) caused profound changes in bicarbonate absorption in the early PCT (169 +/- 25 and -187 +/- 15 peq/mm X min, respectively). Because the bicarbonate absorptive capacity of the early PCT under free-flow conditions is 500 peq/mm X min, angiotensin II administration or inhibition affected greater than 60% of proton secretion in this segment. Both agents less markedly affected bicarbonate absorption in the late PCT (+/- 28 peq/mm X min) or chloride absorption (+/- 68-99 peq/mm X min) in both the early and late PCT. Because of its potential for controlling the majority of bicarbonate absorption in the early PCT (hence greater than or equal to 30% of bicarbonate absorption in the entire nephron), angiotensin II may be a powerful physiologic regulator of renal acidification.     

Evidence for neutral transcellular NaCl transport and neutral basolateral chloride exit in the rabbit proximal convoluted tubule.

The electrical nature of active NaCl transport and the significance of a basolateral membrane chloride conductance were examined in isolated perfused rabbit proximal convoluted tubules (PCT). PCT were perfused with a high chloride solution that simulated late proximal tubular fluid and were bathed in an albumin solution that simulated rabbit serum in the control and recovery periods. The electrical nature of NaCl transport was examined by bathing the tubules in a high chloride albumin solution where there were no anion gradients. Volume reabsorption (Jv) during the control and recovery period was 0.56 and 0.51 nl/mm X min, respectively, and 0.45 nl/mm X min when the tubules were bathed in a high chloride bath. The transepithelial potential difference (PD) during the control and recovery periods averaged 2.3 mV, but decreased to 0.0 mV in the absence of anion gradients, which indicated that NaCl transport is electroneutral. Further evidence that NaCl transport is electroneutral was obtained by examining the effect of addition of 0.01 mM ouabain in PCT perfused and bathed with high chloride solutions. The Jv was 0.54 nl/mm X min in the control period and not statistically different from zero after inhibition of active transport. The PD was not different from zero in both periods. Two groups of studies examined the role of basolateral membrane Cl- conductance in NaCl transport. First, depolarizing the basolateral membrane with 2 mM bath Ba++ did not significantly affect Jv or PD. Second, the effect of the presumptive Cl- conductance inhibitor anthracene-9-CO2H was examined. Anthracene-9-CO2H did not significantly affect Jv or PD. In conclusion, these data show that NaCl transport in the PCT is electroneutral and transcellular and provide evidence against a significant role for basolateral membrane chloride conductance in the rabbit PCT.     

Intracellular cystine loading inhibits transport in the rabbit proximal convoluted tubule.

Cystinosis is an autosomal recessive disorder characterized by a high intracellular cystine concentration. To establish an in vitro model of this disorder and examine the mechanism of the proximal tubule transport defect seen with elevated intracellular cystine concentrations, rabbit proximal convoluted tubules (PCT) were perfused in vitro. PCTs were loaded with cystine using cystine dimethyl ester, a permeative methyl ester derivative. Bath cystine dimethyl ester (0.5 mM) reduced volume absorption (Jv) (0.67 +/- 0.07 to 0.15 +/- 0.09 nl/mm.min, P less than 0.01), bicarbonate transport (JTCO2) (47.2 +/- 4.9 to 11.1 +/- 2.8 pmol/mm.min, P less than 0.001) and glucose transport (JGLU) (34.1 +/- 1.5 to 19.7 +/- 1.5 pmol/mm.min, P less than 0.001). The methyl esters of leucine (0.5 mM), and tryptophan (0.5 and 2.0 mM) had no effect on these parameters. To examine if intracellular reduction of cystine to cysteine could contribute to the inhibition in transport, the effect of bath cysteine methyl ester on proximal tubular transport was examined. Bath cysteine methyl ester (2 but not 0.5 mM) resulted in an inhibition in Jv, JGLU, and JTCO2. Cystine dimethyl ester had no effect on mannitol or bicarbonate permeability. These data are consistent with intracellular proximal tubular cystine accumulation resulting in an inhibition of active transport.     

Defective dopamine-1 receptor adenylate cyclase coupling in the proximal convoluted tubule from the spontaneously hypertensive rat.

The natriuretic effect of DA-1 agonists is less in the spontaneously hypertensive rat (SHR) than its normotensive control, the Wistar-Kyoto rat (WKY). To determine a mechanism of the decreased effect of DA-1 agonists on sodium transport, DA-1 receptors in renal proximal convoluted tubule (PCT) were studied by radioligand binding and by adenylate cyclase (AC) determinations. Specific binding of 125I-SCH 23982 (defined by 10 microM SCH 23390, a DA-1 antagonist) was concentration dependent, saturable, and stereoselective. The dissociation constant, maximum receptor density, and DA-1 antagonist inhibition constant were similar in SHR and WKY. The apparent molecular weight of the DA-1 receptor determined by the photoaffinity D1 probe 125I-MAB was also similar in WKY and SHR. However, DA-1 agonists competed more effectively for specific 125I-SCH 23982 binding sites in WKY than in SHR. Basal as well as forskolin, parathyroid hormone, GTP and Gpp(NH)p-stimulated-AC activities were similar. In contrast DA-1 agonists (fenoldopam, SKF 38393, SND 911C12) stimulated AC activity to a lesser extent in SHR. GTP and Gpp(NH)p enhanced the ability of DA-1 agonists to stimulate AC activity in WKY but not in SHR. These data suggest a defect in the DA-1 receptor-second messenger coupling mechanism in the PCT of the SHR.     

Modulation of phosphate absorption by calcium in the rabbit proximal convoluted tubule.

Proximal convoluted (S2) and straight (S3) renal tubule segments were studied to determine the effect of Ca on lumen-to-bath phosphate flux (JlbPO4). Increasing bath and perfusate Ca from 1.8 to 3.6 mM enhanced JlbPO4 from 3.3 +/- 0.7 to 6.6 +/- 0.6 pmol/mm per min in S2 segments (P less than 0.001) but had no effect in S3 segments. Decreasing bath and perfusate Ca from 1.8 to 0.2 mM reduced JlbPO4 from 3.7 +/- 0.6 to 2.2 +/- 0.6 in S2 segments. These effects were unrelated to changes in fluid absorption and transepithelial potential difference. Increasing cytosolic Ca with a Ca ionophore, inhibiting the Ca-calmodulin complex with trifluoperazine, or applying the Ca channel blocker nifedipine had no effect on JlBPO4 in S2 segments. Increasing only bath Ca from 1.8 to 3.6 mM did not significantly affect JlbPO4. However, increasing only perfusate Ca enhanced JlbPO4 from 3.4 +/- 0.7 to 6.1 +/- 0.7 pmol/mm per min (P less than 0.005). Inhibition of hydrogen ion secretion, by using a low bicarbonate, low pH perfusate, both depressed base-line JlbPO4 and abolished the stimulatory effect of raising perfusate Ca. Net phosphate efflux (JnetPO4) also increased after ambient calcium levels were raised, ruling out a significant increase in PO4 backflux. When net sodium transport was abolished by reducing the bath temperature to 24 degrees C, JnetPO4 at normal ambient calcium was reduced and increasing ambient calcium failed to increase it, ruling out a simple physicochemical reaction wherein phosphate precipitates out of solution with calcium. The present studies provide direct evidence for a stimulatory effect of Ca on sodium-dependent PO4 absorption in the proximal convoluted tubule, exerted at the luminal membrane. It is postulated that Ca modulates the affinity of the PO4 transporter for the anion.     

Chronic metabolic acidosis causes an adaptation in the apical membrane Na/H antiporter and basolateral membrane Na(HCO3)3 symporter in the rat proximal convoluted tubule.

The effect of chronic dietary acid on the apical membrane Na/H antiporter and basolateral membrane Na(HCO3)3 symporter was examined in the in vivo microperfused rat proximal tubule. Transporter activity was assayed with the epifluorescent measurement of cell pH using the intracellular, pH-sensitive fluorescent dye, (2'7')-bis(carboxyethyl)-(5,6)-carboxy-fluorescein (BCECF). BCECF was calibrated intracellularly, demonstrating similar pH-sensitivity of the dye in control and acidotic animals. In subsequent studies, lumen and peritubular capillaries were perfused to examine Na/H and Na(HCO3)3 transporter activity in the absence of contact with native fluid. The initial rate of change in cell pH (dpHi/dt) was 97, 50, and 44% faster in tubules from acidotic animals when peritubular [HCO3] was changed from 25 to 10 mM in the presence or absence of chloride, or peritubular [Na] was changed from 147 to 50 mM, respectively. dpHi/dt was 57% faster in tubules from acidotic animals when luminal [Na] was changed from 152 to 0 mM. Buffer capacities, measured using NH3/NH+4 addition, were similar in the two groups. The results demonstrate that chronic metabolic acidosis causes an adaptation in the intrinsic properties of both the apical membrane Na/H antiporter and basolateral membrane Na(HCO3)3 symporter.     

Cell pH in the rat proximal convoluted tubule. Regulation by luminal and peritubular pH and sodium concentration.

To examine the relative roles of apical and basolateral membrane transport mechanisms in the regulation of cell pH in the proximal convoluted tubule, cell pH was measured in the in vivo microperfused rat tubule using fluorescence. Decreasing luminal pH by 0.7 pH units caused cell pH to decrease by 0.08 pH units, whereas a similar decrease in peritubular pH caused cell pH to decrease by 0.32 pH units. Inhibition of basolateral membrane bicarbonate transport with peritubular 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS) enhanced the response to luminal fluid acidification. Removal of luminal sodium caused a small transient acidification which was followed by a late alkalinization. Peritubular SITS increased the magnitude of the transient acidification, and eliminated the late alkalinization. The acidification was partially inhibited by luminal amiloride. The results demonstrate sodium-coupled processes on both the apical (Na/H antiport) and basolateral (Na/HCO3 symport) membranes. Basolateral membrane transporters are more important determinants of cell pH.     

Novel amiloride-sensitive sodium-dependent proton secretion in the mouse proximal convoluted tubule

The proximal convoluted tubule (PCT) reabsorbs most of the filtered bicarbonate. Proton secretion is believed to be mediated predominantly by an apical membrane Na(+)/H(+) exchanger (NHE). Several NHE isoforms have been cloned, but only NHE3 and NHE2 are known to be present on the apical membrane of the PCT. Here we examined apical membrane PCT sodium-dependent proton secretion of wild-type (NHE3(+/+)/NHE2(+/+)), NHE3(-/-), NHE2(-/-), and double-knockout NHE3(-/-)/NHE2(-/-) mice to determine their relative contribution to luminal proton secretion. NHE2(-/-) and wild-type mice had comparable rates of sodium-dependent proton secretion. Sodium-dependent proton secretion in NHE3(-/-) mice was approximately 50% that of wild-type mice. The residual sodium-dependent proton secretion was inhibited by 100 microM 5-(N-ethyl-N-isopropyl) amiloride (EIPA). Luminal sodium-dependent proton secretion was the same in NHE3(-/-)/NHE2(-/-) as in NHE3(-/-) mice. These data point to a previously unrecognized Na(+)-dependent EIPA-sensitive proton secretory mechanism in the proximal tubule that may play an important role in acid-base homeostasis.     

Basolateral membrane Na+/H+ antiport, Na+/base cotransport, and Na+-independent Cl-/base exchange in the rabbit S3 proximal tubule.

The basolateral membrane Na+ and Cl(-)-dependent acid-base transport processes were studied in the isolated perfused rabbit S3 proximal straight tubule. Intracellular pH (pHi) was measured with 2'7'-biscarboxyethyl-5,6-carboxyfluorescein (BCECF) and a microfluorometer coupled to the tubule perfusion apparatus. Reduction of basolateral HCO3- from 25 to 5 mM caused pHi to decrease at a rate of 0.81 pH/min. Approximately 50% of this rate was Na+-dependent, 30% Cl(-)-dependent and 20% Na+ and Cl(-)-independent. Two basolateral Na+-dependent acid base transport pathways were detected: (a) an amiloride-sensitive Na+/H+ antiporter and (b) a stilbene-sensitive Na+/base cotransporter. No evidence was found for a Na+-dependent Cl-/base exchanger. The Cl(-)-dependent component of basolateral base efflux was mediated by a stilbene-sensitive Na+-independent Cl-/base exchange pathway. The results suggest that the acid base transport pathways of the basolateral membrane of the S3 proximal tubule differ from more proximal nephron segments.     

Axial heterogeneity of bicarbonate, chloride, and water transport in the rat proximal convoluted tubule. Effects of change in luminal flow rate and of alkalemia.

These studies examined regulation of superficial proximal convoluted tubule (PCT) transport as a function of length. When single nephron glomerular filtration rate (SNGFR) increased from 28.7 +/- 0.7 nl/min in hydropenia to 41.5 +/- 0.4 nl/min in euvolemia, bicarbonate, chloride, and water reabsorption in the early (1st mm) PCT increased proportionally: from 354 +/- 21 peq/mm X min, 206 +/- 55 peq/mm X min, and 5.9 +/- 0.4 nl/mm X min to 520 +/- 12 peq/mm X min, 585 +/- 21 peq/mm X min, and 10.1 +/- 0.4 nl/mm X min, respectively. These high transport rates did not increase further, however, when SNGFR went to 51.2 +/- 0.7 or 50.7 +/- 0.6 nl/min after atrial natriuretic factor or glucagon administration. Anion and water transport rates in the late PCT were lower and exhibited less flow dependence. During chronic metabolic alkalosis, acidification was inhibited in the late but not early PCT. In conclusion, the early PCT is distinguished from the late PCT by having high-capacity, flow-responsive but saturable, anion- and water-reabsorptive processes relatively unaffected by alkalemia.