Journal of Clinical InvestigationVol. 43, No. 10, 1964

Effect of Potassium Deficiency on the Reabsorption of Bicar-bonate in the Proximal Tubule of the Rat Kidney *

FLOYD C. RECTOR, JR., H. ALLAN BLOOMER,t ANDDONALDW. SELDIN WITH THE

TECHNICALASSISTANCEOF MARTHAHUDDLESTON

(From the Department of Internal Medicine, the University of Texas Southwestern Medical

School, Dallas, Texas)

Potassium deficiency accelerates the secretion ofHI ions by the kidney; in consequence the net ex-cretion of acid (ammonia and titratable acid-bi-carbonate) into the urine and the capacity to re-absorb filtered HCO3- are increased (1-7). Al-though the precise mechanism involved has notbeen identified, Berliner, Kennedy, and Orloff (8),on the basis of the demonstrated reciprocal re-lationship between H4 and K+ secretion, proposedthat these ions compete for a common secretorypathway in the distal nephron. Consequently, K+depletion, by lowering the concentration of K+ atthe competitive secretory site, would facilitate H+secretion and increase the capacity of the distaltubule to reabsorb HCO3- (9).

Certain observations, however, are difficult toreconcile with the theory of competitive inhibition.Rector, Buttram, and Seldin (10) found that theinhibitory effects of Ki administration on HCO3-reabsorption could not be overcome by raising in-tracellular H4 concentration by respiratory acido-sis. This observation, which is not consistent withthe theory of competitive inhibition between H+and K+, suggests that K4 might reduce Hi secre-tion by either noncompetitive inhibition or by alka-linizing the renal tubular cells. If alterations ofintracellular K+ were capable of changing the pHof renal tubular cells, two consequences might fol-low: first, the inverse relationship between H+ and

* Submitted for publication May 4, 1964; accepted June24, 1964.

Supported in part by U. S. Public Health Servicegrants HTS-5469 and 2A-5028 and in part by an Ameri-can Heart Association grant.

t Work done during the tenure of a fellowship of theU. S. Public Health Service, grants HTS-5469 and2A-5028. Present address: Department of InternalMedicine, University of Utah College of Medicine, SaltLake City, Utah.

K+ secretion could be the result of reciprocalchanges in the intracellular concentrations of thesetwo ions in the distal nephron, rather than compe-tition for a common secretory pathway; second,by altering the pH of proximal tubular cells,changes in intracellular K+ might influence H+secretion even though this area of the nephron isnot a site of K+ secretion.

The present experiments in rats were designedto investigate whether K+ deficiency accelerates HWsecretion in the distal nephron only, where K+ isknown to be secreted ( 11), or also in the proximaltubule, where we (12), as well as others (11, 13),have demonstrated that K+ is reabsorbed but notsecreted. If the HCO3- reabsorptive capacity ofthe distal, but not the proximal tubule, were in-creased, the concentration of HCO3- in plasmaand in glomerular filtrate would be maintained ata concentration far above the proximal reabsorp-tive capacity. Consequently, as NaCl and H20were reabsorbed in the proximal tubule, the con-centration of the unreabsorbed bicarbonate wouldrise, and proximal tubular fluid would becomemore alkaline than blood. In contrast, if theHCO,- reabsorptive capacity of the proximal tu-bule were increased either alone or with a propor-tionate increase in distal reabsorptive capacity, theconcentration of HCO3- in plasma and glomerularfiltrate would be maintained at a level near, butnot exceeding, the proximal reabsorptive capacity.Therefore, the relative rates of NaHCO3, NaCl,and H20 reabsorption would be similar to thoseof normal rats, and the concentration of HCO,-in proximal fluid should fall below that in plasma,as it does normally. These two possibilities wereexamined by comparing the concentration ofHCO3- in proximal tubular fluid in IK+-deficient,alkalotic rats with that in normal rats and in ratsma(le acutely alkalotic by an infusion of NaHCO:,.

1976

EFFECT OF POTASSIUMDEFICIENCY ON RENAL BICARBONATEREABSORPTION

TABLE I

Treatment and plasma composition of the experimental groups

Plasma*

No. of C02Group rats Treatment [K] p)H content Pco2

mEq,/L mEqIL mmHg

Normal 10 None 4.5 7.39 26.6 40±0.2 ±0.04 ±2.5 ±2

IINaHCO3 11 0.15 MNaHCO3infu- 3.8 7.57 39.8 45

sion for 2 hours ±0.2 ±0.05 ±3.5 ±3

IIIPotassium- 17 SEDDt + Na2SO4 1.7 7.55 38.3 44

deficient + DOCAI for 7 days ±0.3 ±0.03 ±2.3 ±3

* Mean values ± SD.t Standard electrolyte-deficient diet.t Desoxycorticosterone acetate.

MethodsMicropuncture studies were performed on three groups

of male Sprague-Dawley rats. Groups I and II were fedrat pellet diet and tap water. Group I received no fur-ther treatment. Group II rats were infused with 0.15 MNaHCO3at the rate of 0.1 ml per minute for 2 hoursbefore collecting any samples of tubular fluid; the infu-sion was continued during the collection periods. This2-hour infusion period permitted the blood pH andplasma HCO3- concentrations to attain reasonably stablevalues. Group III rats were made K+ deficient by feed-ing them a standard electrolyte-deficient diet containing1 mMNa2SO4 daily and injecting. 5 mg desoxycorticos-terone acetate (DOCA) in oil intramuscularly daily for7 days. All animals were fasted for 18 hours before theexperiment to permit complete excretion of the dietaryNa2SO4; the last injection of DOCAwas 24 hours beforethe micropuncture study.

The rats were anesthetized with sodium pentobarbitaland prepared for micropuncture as previously described(12), except that the left kidney was exposed througha flank incision. Samples of tubular fluid were aspiratedinto quinhydrone microelectrodes for the measurement ofpH. The site of collection was determined by micro-dissection after injecting the tubule with latex. At theend of the experiment blood was collected from the ab-dominal aorta for measurement of pH, C02 content, andK .

The concentration of HCO3- in tubular fluid was esti-mated by the following technique. The pH of tubularfluid was measured with quinhydrone microelectrodesprepared as described by Pierce and Montgomery (14).Immediately before use the microelectrodes were filledwith mineral oil that had been equilibrated with 5% C02.Samples aspirated into the tip of the pipette-electrodequickly equilibrated to the same Pco2 as the mineral oil.The electrode tips were sealed by dipping them into eggalbumin. The voltage difference between the quinhy-

drone electrode and a saturated KCl-calomel referenceelectrode was measured at 370 C, with a General-Radioelectrometer. The pH was calculated from the formulagiven by Pierce and Montgomery (14). Since the pH ofthese samples was measured at a constant Pco2 of ap-proximately 40 mmHg in the electrode rather than atthe actual Pco2 of plasma, the measured value was notthe true intratubular pH, but represented instead ameasure of the HC03- concentration in the tubular fluid(15). The concentration of HCO3- in tubular fluid wascalculated from the quinhydrone pH and the known Pco2of the mineral oil in the electrode by the Henderson-Hasselbalch equation.

In an additional series of experiments in four ratsmade alkalotic by NaHCO3 infusion, the effect of acutereductions in glomerular filtration rate (GFR) on proxi-mal acidification was investigated. Proximal HCO3-concentration was measured in the same tubule beforeand after constricting the aorta above the renal arteries.A silk ligature was passed around the aorta and threadedthrough a small glass capillary tube; when the ligatureprotruding from the capillary was tied around a smallglass rod and twisted, the aorta was gently pulled against

Tubular FluidBicarbonate

ConcentrationmET/L

50302010

53

2

I1

%PROXIMAL TUBULE25 50 75 10o

%v/STAL UIJNE0 50 o00

I --I m--l

Mean Ptasma Bicarborole

.

0.3FFic.. 1. CONCENTRATION OF BICARBONATE IN TUTBLAR

FLUID AND URINE TN NORMALRATS.

1977

F. C. RECTOR, JR., H. A. BLOOMER,AND D. W. SELDIN

'7o ProximacS 7 Dif'cdZ0 25 50 75 0OO 0 50 100

I I

_ . @ .. Air: *___ 0_2 __*____

Mcan Plasmct Z3icdrbondie

SOFu

FIG. 2. CONCENTRATIONOF BICARBONATE IN TUBULAR FLUID AND URINE IN

RATS INFUSED WITH 0.15 M NAHCO3FOR 2 HOURS.

the glass tube. The degree of constriction was moni-tored by measuring the femoral blood pressure througha small polyethylene cannula with a Statham straingauge and a Sanborn Twin-Viso recorder. Preliminaryexperiments established that reducing femoral bloodpressure to approximately 60 mmHg lowered GFR by50 to 65%. During the control periods 0.15 M NaHCO3was infused at a rate of 0.1 ml per minute and inulin at a

rate of 1 mg per minute; after aortic constriction the in-fusion rates were reduced to 0.05 ml per minute forNaHCO3and 0.5 mg per minute for inulin. Before andafter aortic constriction blood was sampled from thejugular vein, and timed urine samples were collectedfrom a bladder catheter for the measurement of inulin,pH, and C02 content.

Blood and urine pH were measured in a Beckmananaerobic glass electrode at 370 C with a Vibron pHmeter. The C02 contents were measured by the Natelsonmicrogasometer. Serum K+ was determined by an in-ternal standard flame photometer. Inulin in blood andurine was measured by the method of Walser, Davidson,and Orloff (16).

100

807060

Proximal 50

B3icarbonate 40Gorncentraf ton

mEq/L 30

- rps C=.

Mean Plasma BitcarEbonate

tConlrot

tAfter

AorLicConstriction

0 20 40 60 80

%O Reduction in GFR

FIG. 3. EFFECT OF ACUTE REDUCTIONS IN GLOMERULAR

FILTRATION RATE (GFR) ON PROXIMAL BICARBONATECON-

CENTRATION IN RATS INFUSED WITH NAHCO3. The bi-

carbonate concentrations from the same tubule before andafter aortic constriction are connected by the solid lines.

Only measurements from the middle third of the tubuleare shown.

Results

The plasma composition of the three groups isshown in Table I. At the end of the micropunc-ture experiments the rats in group 1 had valuesfor blood pH, plasma PCO2 content, and K+ con-

centration that were very similar to those obtainedin rats in our laboratory not subjected to the mi-cropuncture procedures. In group II the infusionof 0.15 MNaHCO3for 2 hours before and duringthe experiment resulted in a severe metabolic al-kalosis: blood pH of 7.57 + 0.05 (SD), plasmaCO2 content of 39.8 3.5 mmoles per L, and

plasma Pco2 of 45 3 mmHg. As expected,acute metabolic alkalosis caused a slight fall inthe concentration of plasma K+ to 3.8 0.2 mEqper L. In group III the severe hypokalemia of

1.7 0.3 mEqper L was associated with a marked

metabolic alkalosis, with an acid-base compositionalmost identical to that in group II: blood pH,7.55 0.03; plasma CO2 content, 38.3 + 2.3

mmoles per L; and plasma PCo2, 44 + 3 mmHg.The concentration of HCO,- in tubular fluid and

too

5030

20Tubular FluidBtcarbonate

ConcenfrafCon 5mEq1i. 3

:2

03F

96 PROXIMAL TUIULE 01. DISTAL URINE25 50 '75 100 0 100

I ,I F- rn, , m

MAean Plazma 8itcarbonals

_ :0 *.o -

0we

sc **

"

0* I

FIG. 4. CONCENTRATION OF BICARBONATE IN TUBULAR

FLUID AND URINE IN POTASSIUM-DEFTCIENT RATS.

200

Tubutar FluidBicarboncdu

ConcenrvaionmEq/L

1007050

30

UrineM~

1978

EFFECT OF POTASSIUMDEFICIENCY ON RENAL BICARBONATEREABSORPTION

urine in the normal rats (group I) is shown inFigure 1. The concentration of HC03- in proxi-mal tubular fluid progressively fell, reaching val-ues as low as 5 mEqper L. The average HCO3-concentration in the middle third of the proxi-mal tubule was 7.5 + 2.2 mEq per L. These re-sults are similar to those reported by Gottschalk,Lassiter, and Mylle (17).

In the rats made acutely alkalotic by the infu-sion of NaHCO3 (group II), the concentrationof HCO3j in proximal tubular fluid rose to a levelsignificantly higher than that in plasma (Figure2). In the middle third of the proximal tubulethe HC03- concentration in every sample washigher than in plasma, averaging 57.8 + 13.5 mEqper L.

Acutely lowering GFRhad no effect on proxi-mal bicarbonate concentration in the rats givenNaHCO3 (Figure 3). Aortic constriction re-duced the GFRby 50 to 60%. Blood pH, CO2content, and Pco2 were the same before and afteraortic constriction. Despite the marked reductionin GFRthe concentration of HC03- in individualproximal tubules was essentially the same afteraortic constriction as before.

In contrast to results obtained in the acutelyalkalotic rats, the concentration of HCO3- inproximal tubular fluid in the rats with hypokalemicalkalosis was lower than in plasma (Figure 4).In the middle third of the proximal tubule theHC03- concentration of every sample was lowerthan that of plasma, falling from a mean con-centration of 37.2 ± 2.3 mEq per L in plasma toa mean concentration of 17.8 ± 7.5 mEqper L in

TABLE II

Effect of potassium deficiency on acidificationof proximal tubular fluid

Plasma Proximal tubule*

Grouip pH [HCO3-1 pHt [HCO3-]

mrEq/lmLq/L

I 7.39 25.4 6.88 7.5Normal 4±0.04 2.5 ±0.12 ±2.2

II 7.57 38.5 7.75 57.8NaHCO3 ±0.05 ±3.5 ±0.15 ±13.5

III 7.55 37.2 7.15 17.8Potassium- i0.03 ±2.3 ±0.27 ±7.5

deficient

* Mean ± SD in middle third of proximal tubule.t Quinhydrone pH of sample equilibrated with 5% Co2.

tubular fluid (Table II). The fluid entering thedistal tubule contained almost no HC03-, indi-cating that virtually all the filtered HC03- hadbeen reabsorbed in more proximal segments ofthe nephron.

Discussion

In the normal rat filtered HC03- is reabsorbedin the proximal convoluted tubule at a rate rela-tively faster than the isosmotic reabsorption ofwater; consequently the concentration of HC03-in the fluid issuing from the proximal tubule isless than that of plasma. In contrast, duringacute alkalosis the concentration of HC03- inplasma and glomerular filtrate exceeds the proxi-mal reabsorptive capacity, so that as water is reab-sorbed isosmotically (secondary to NaCl reab-

sorption), the unreabsorbed HC03- is ConCell-trated to a level above that in plasma.

These results clearly indicate that the concen-

tration of HC03- in the fluid leaving the proximaltubule is determined not only by the rate of HC03-reabsorption (RNaHCo3), but also by the rate ofwater reabsorption and the concentration ofHCO,- in glomerular filtrate ([HCO3j GF).Since NaCl and NaHCO3are the principal os-motically active solutes whose removal promotesthe isosmotic reabsorption of water, the directionalchanges in the HC03- concentration in tubularfluid ([HCO3 ]TF) can best be expressed interms of the relative rates of NaCl and NaHCO3reabsorption. For purposes of this discussion, theterm relative rate is defined as the rate of reab-sorption of a particular sodium salt divided by itsconcentration in glomerular filtrate. The rela-tive rates for NaCl and NaHCO3reabsorption are

RNaCl/[NaClIGF and RNaHCO3/[NaHCO3]OGF, re-

spectively.If the relative rates of NaCl and NaHCO3re-

absorption were equal, [Cl-]TF and [HCO;3]TFwould not change, remaining equal to their con-

centrations in plasma and glomerular filtrate. If,on the other hand, the relative rate for NaHCO3were greater than that for NaCl, [HCO,-aITFwould fall below and [Cl-]TF would rise abovetheir respective concentrations in plasma, whereasif the relative rate for NaHCO3were less thanthat for NaCl, then [HCO3j TF would rise and[ClI]TF would f all.

1979

F. C. RECTOR, JR., H. A. BLOOMER,AND D. W. SELDIN

Changes in [NaHCO0] GF and [NaCi] GF wouldinfluence the directional change in [HCO3 ]TFonly if RNaHco3 and RNaC1 were not linearly re-lated to [NaHCO3]GF and [NaCl] GF- IfRNaHCO3 and RNaC1 were both linearly related to[NaHCO3]GF and [NaCl]GF, respectively, thenthe relationship between RNaHCO3/[NaHCO3] GFand RNaC1/[NaCl]GF obviously would not changeas the composition of the:-glomerular filtrate wasaltered. From currently available micropuncturedata RNaC, does in fact appear to be a linear func-tion of [NaCl] GF. Giebisch, Klose, and Wind-hager (18) and Lassiter, Gottschalk, and Mylle(19) found that raising [NaCl] GF by the infusionof 5% saline resulted in proportionate increases inRNaCl. Clearance studies, however, clearly re-veal that the over-all tubular reabsorption ofNaHCO3 does not increase linearly as [Na-HCO3] GF is elevated and, instead, exhibits a reab-sorptive maximum (20). The present studiesalso indicate that proximal RNaHCO3is a nonlinearfunction of [NaHCO3]GF; therefore, changes in[NaHCO3] GF do alter the directional changes inproximal [ HC03-] TF-

In the normal rats [HCO3-] TF in proximaltubular fluid fell below that in plasma to a levelof about 7.5 mEq per L. Thus, in these normalrats, the relative rate of NaHCO3 reabsorptionexceeded that for NaCl. As [NaHCO3] GF wasacutely elevated by the infusion of NaHCO3, thedirectional change in [HCOj-] TF reversed, and[HCO3-] TF rose to approximately 58 mEqper Lor roughly 1.5 times the concentration in plasmaand glomerular filtrate. In the acutely alkaloticrats, therefore, the relative rate of NaHCO3re-absorption was less than that for NaCl. Thisclearly indicates that RNaHCO3did not increase inlinear fashion as [NaHCO3] GF was raised, butinstead exhibited saturation kinetics.

Potassium deficiency obviously altered the re-sponse of proximal RNaHCO3 to increased (Na-HCO3]IGF. At the same high [NaHCO3] GFas was present in the rats given NaHCO3 (Ta-ble II), [HCO3] TF fell below that in plasma andglomerular filtrate. The relative rate of NaHCO3reabsorption, therefore, exceeded that for NaCldespite the high [NaHCO3]GF* Since the [Na-HCO3]GF and [NaCl]GF were approximately thesame in the K+-deficient rats and the rats infusedwith NaHCO3, the reabsorptive ratio RNaHCO3/

RNaC1 must have been greater in the K+-deficientthan in the acutely alkalotic rats.

Several factors might have been responsible forthe relative increase in proximal NaHCO3 reab-sorption in the K+-deficient rats. Holliday, Eagan,and Wirth (21) have reported that K+ deficiencydepresses the GFR in rats. It is conceivable,therefore, that the increased proximal acidificationin the K+-deficient rats might have been the con-sequence of a fall in GFR. On an a priori basis,however, it is difficult to predict the effect of re-duced GFRon proximal acidification, since clear-ance studies on intact animals have demonstratedthat the reabsorption of both NaCl (22) andNaHCO3 (20) tend to decrease as GFR falls.Such studies, however, do not indicate the relativecontributions of the proximal and distal nephron,nor do they establish the relative magnitudes inthe reduction in NaCl and NaHCO3reabsorptionas GFRis decreased. For a reduction in GFRtoaccount for the proximal acidification in the K+-deficient rats, it would be necessary that RNac, bedepressed to a greater extent than RNaHCO3, so thatthe reabsorptive ratio RNaHCO3/RNaCl is increased.Therefore, to elucidate the role of GFR, if alny,in proximal acidification, GFRwas reduced 50 to60% by constricting the aorta in rats made acutelyalkalotic by an infusion of NaHCO3 (Figure 3).Despite these marked reductions in GFR the tu-bular fluid remained alkaline. This must meanthat a reduction in GFR depresses RNaCl andRNaHCO3to the same extent and therefore cannotlower the concentration of HCO3- in proximal tu-bular fluid. It is concluded that acidification ofproximal tubular fluid in K+ deficiency cannot bedue to a fall in GFR.

Since variations in plasma CO2 tension areknown to influence the capacity to reabsorb filteredHC03-, the mild hypercapnia (Table I) observedin the hypokalemic rats might account in part forthe relative increase in RNaHCo3. However, thiscannot account for the relatively greater RNaHCO3in the hypokalemic rats, since the plasma CO2 ten-sions were identical in the rats made alkaloticwith NaHCO3and the rats with hypokalemic alka-losis (Table I). These experiments indicate,therefore, that K+ deficiency per se is in someway responsible for the increased RNaHCO3relativeto RNaC1 in the proximal convoluted tubule.

Potassium deficiency might augment the rate

1980

EFFECT OF POTASSIUMDEFICIENCY ON RENAL BICARBONATEREABSORPTION

of NaHCO3 relative to NaCl reabsorption inone of several ways. One possibility is that,rather than a primary increase in the rate ofNaHCO3 reabsorption, the rate of NaCl reab-sorption is decreased. The reabsorption of NaClis thought to be mediated by an ion exchangepump at the peritubular surface of the cell thatpumps Na+ out of K+ into the cell, with Cl-moving passively from lumen to blood (23).It is conceivable, therefore, that a decreased con-centration of K+ in blood would decrease the rateof Na+ transport out of the cell and consequentlydecrease NaCl reabsorption. Giebisch and Wind-hager (24) have reported that lowering the con-centration of K+ in peritubular fluid decreased therate of proximal Na+ reabsorption in Necturus.Bank and Aynedjian (25), however, have recentlyfound that the percentage of glomerular filtratereabsorbed in the proximal tubules of K+-deficientrats is increased. Unfortunately, this study, whilesuggestive, is not conclusive; the GFR was re-duced in the animals studied by Bank and Ayned-jian, so that their results do not necessarily ex-clude a decrease in the rate of NaCl reabsorption.More important, however, is the fact that K+ defi-ciency not only augments proximal acidificationbut also increases the absolute rate of NaHCO3reabsorption (3, 7). Therefore, while a primarydecrease in RNaC1 could account for the fall inproximal [HCO;] TF, it could not account for thegreatly augmented HCO.- reabsorptive capacityassociated with Ki depletion.

It is much more probable, therefore, that theeffects of K+ deficiency on proximal acidificationare a reflection of an increase in the rate of H+secretion. Since it has previously been shownthat K+ is reabsorbed (11-13), but not secreted inthe proximal tubule, this effect cannot be due tocompetition between H+ and K+ at a commonsecretory site on the luminal surface of the cell.Although it is possible that K+ inhibits H+ secre-tion by some noncompetitive process, it is morelikely that K+ influences H+ secretion by changingthe pH of renal tubular cells. Anderson andMudge (26) demonstrated that in kidney slicesHCO3- moves into or out of the cells togetherwith K+. Thus, K+ deficiency might decrease thesteady-state concentration of HCO3- in the tubu-lar cells so that at any given Pco2 there would bea lower intracellular pH. As a result of this in-

crease in intracellular HI concentration, the se-cretion of H4 would be stimulated, thereby aug-menting the rate of NaHCO, reabsorption.

Potassium deficiency might lower the steady-state concentration of HCO3- in the tubular cellsby accelerating the rate of removal of HCO3- ions.According to current concepts, the HCO3- gen-erated in the cell by the combination of H2CO3formation and H4 secretion moves out of the cellalong electrochemical gradients. An importantfactor in HCO- removal, therefore, would bethe potential difference across the peritubularmembrane. Wehave found that the resting mem-brane potential of skeletal muscle increases froma mean value of 89 + 1 .(SD) mv in normal ratsto 97 + 3 mv in K+-deficient rats (27). If simi-lar changes in potential difference occurred acrossthe peritubular surface of the renal epithelial cells,the electrical force driving HCO3- out of the cellwould be commensurately increased and couldtherefore result in a decreased steady-state intra-cellular concentration of HCO3-.

Although it is tempting to speculate that K+ de-ficiency affects the proximal and distal tubules ina similar fashion, these experiments cast no lighton the relation between K+ and H+ secretion inthe distal nephron. The conclusion that K+ de-ficiency augments H+ secretion in the proximaltubule by lowering intracellular pH cannot be ex-trapolated to the distal nephron where competitionbetween K+ and Hf for a common secretory path-way may well be operative.

Summary

Proximal acidification was investigated by meas-uring HCO3- concentration in tubular fluid innormal rats, rats made acutely alkalotic by an in-fusion of NaHCO3, and rats with hypokalemicalkalosis. The concentration of HCO3- in theproximal tubule of normal rats fell to an averagevalue of 7.5 mEqper L, a value significantly lowerthan that of plasma. Despite a comparable de-gree of metabolic alkalosis in the rats given Na-HCO3and the hypokalemic rats, every sample ofproximal fluid in the rats given NaHCO3had ahigher HC03- concentration than plasma, whereasevery proximal sample in the hypokalemic ratshad a lower HCO3 concentration than plasma.This clearly indicates that Ki deficiency increases

1981

F. C. RECTOR, JR., H. A. BLOOMER,AND D. W. SELDIN

the capacity of the proximal convoluted tubule toreabsorb filtered HCO3-. Since K+ is not se-creted in the proximal tubule, the effect of K+ de-ficiency cannot be due to decreased competitive in-hibition at a common H+-K+ secretory pathway.It is postulated that K+ depletion stimulates proxi-mal H+ secretion by producing an intracellularacidosis.

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3. Roberts, K. E., H. T. Randall, H. L. Sanders, andM. Hood. Effects of potassium on renal tubularreabsorption of bicarbonate. J. clin. Invest. 1955,34, 666.

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5. Iacobellis, M., E. Muntwyler, and G. E. Griffen.Enzyme concentration changes in the kidneys ofprotein- and/or potassium-deficient rats. Amer. J.Physiol. 1954, 178, 477.

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11. Malnic, G., R. M. Klose, and G. Giebisch. Micro-puncture study of renal potassium excretion in therat. Amer. J. Physiol. 1964, 206, 674.

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14. Pierce, J. A., and H. Montgomery. A microquinhy-drone electrode: its application to the determinationof the pH of glomerular urine of Necturus. J.biol. Chem. 1935, 110, 763.

15. Clapp, J. R., J. F. Watson, and R. W. Berliner.Osmolality, bicarbonate concentration, and waterreabsorption in the proximal tubule of the dognephron. Amer. J. Physiol. 1963, 205, 273.

16. Walser, M., D. G. Davidson, and J. Orloff. Therenal clearance of alkali-stable inulin. J. clin. In-vest. 1955, 34, 1520.

17. Gottschalk, C. W., W. E. Lassiter, and M. Mylle.Localization of urine acidification in the mam-malian kidney. Amer. J. Physiol. 1960, 198, 581.

18. Giebisch, G., R. M. Klose, and E. E. Windhager.Micropuncture study of hypertonic sodium loadingin the rat. Amer. J. Physiol. 1964, 206, 687.

19. Lassiter, W. E., M. Mylle, and C. W. GottschalkNet transtubular movement of water and urea insaline diuresis. Amer. J. Physiol. 1964, 206, 669.

20. Pitts, R. F., and W. D.. Lotspeich. Bicarbonate andthe renal regulation of acid base balance. Amer.J. Physiol. 1946, 147, 138.

21. Holliday, M. A., T. Eagan, and P. Wirth. Inulinand free water clearance studies in potassium-deficient rats (abstract). J. Dis. Child. 1958, 96,524.

22. Wesson, L. G., Jr. Glomerular and tubular factorsin the renal excretion of sodium chloride. Medi-cine (Baltimore) 1957, 36, 281.

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1982