Intracellular potential and K+ activity in rat kidney proximal tubular cells in acidosis and K+ depletion

The present studies examined the effect of acute in vitro acidosis on chloride reabsorption in the rabbit cortical thick ascending limb of Henle (cTALH). Four protocols were used: (a) hypercapnic acidosis; (b) "isocapnic" peritubular acidosis (bath bicarbonate reduction to 10 mM); (c) isocapnic luminal acidosis (luminal bicarbonate reduction to 10 mM); (d) isocapnic pentubular acidosis in the absence of luminal potassium. Transepithelial voltage (VT) decreased during hypercapnic acidosis and increased with recovery. Chloride reabsorption (pmol -mm-' v min') decreased from 503±8.4 to 15.7±5.6, then increased to 45.6±11.1 with recovery. Likewise, VT was decreased reversibly during isocapnic peritubular acidosis, and chloride reabsorption decreased by 60%. Chloride reabsorption was greater (283±3.6) when tubules were perfused at normal luminal pH than at an acidotic luminal pH (11.4±4.5; P < 0.05). Luminal potassium removal reduced chloride transport, and acidosis had no significant additional effect. Decreased chloride reabsorption in the cTALH during acidosis could contribute to the chloruresis associated with systemic acidosis. The symmetrical nature of this effect suggests that acidosis inhibits chloride reabsorption through an effect on cytosolic pH.

Section: Resultssupporting

confidence: 75%

Effect of acidosis on chloride transport in the cortical thick ascending limb of Henle perfused in vitro.

Wingo¹

1986

“…The lack of effect on bicarbonate reabsorption in the hypokalemic rats of the present study may have various explanations. Factors likely to stimulate bicarbonate reabsorption that have been defined in the proximal tubule could involve the following: (i) stimulation of Na'-H' exchange, secondary to the intracellular acidosis that has been reported in hypokalemia (42,43) and stimulation of an Hf-sensitive modifier site (44); (ii) activation of basolateral Na'-HCO3 cotransport (45); (iii) hyperpolarization of the basolateral membrane with an increase in the driving force for bicarbonate exit (46). While none of these factors have been identified in any the segments of the LOH, it is probable that they are operative in hypokalemia.…”

Section: Resultsmentioning

confidence: 99%

Bicarbonate transport along the loop of Henle. II. Effects of acid-base, dietary, and neurohumoral determinants.

Capasso¹,

Unwin²,

Ciani³

et al. 1994

The loop of Henle contributes to renal acidification by reabsorbing about 15% of ifitered bicarbonate. To study the effects on loop of Henle bicarbonate transport (JHC03) of acid-base disturbances and of several factors known to modulate sodium transport, these in vivo microperfusion studies were carried out in rats during: (a) acute and chronic metabolic acidosis, (b) acute and chronic (hypokalemic) metabolic alkalosis, (c) a control sodium diet, (d) a high-sodium diet, (e) angiotensin II (AU) intravenous infusion, (f) simultaneously intravenous infusion of both All and the AT1 receptor antagonist DuP 753, (g) acute ipsilateral mechanicochemical renal denervation. Acute and chronic metabolic acidosis increased JHCO3; acute metabolic alkalosis significantly reduced JHCO3, whereas chronic hypokalemic alkalosis did not alter JHCO3. Bicarbonate transport increased in animals on a high-sodium intake and following All administration, and the latter was inhibited by the AII (AT1) receptor antagonist DuP 753; acute renal denervation lowered bicarbonate transport. These data indicate that bicarbonate reabsorption along the loop of Henle in vivo is closely linked to systemic acid-base status and to several factors known to modulate sodium transport. (J. Clin. Invest. 1994. 94:830-838.) Key words: loop

“…With a stoichiometry of three equivalents of HCO3 ions/Na+ ion, membrane depolarization should decrease, whereas hyperpolarization should increase the rate of base extrusion via Na+:CO"-:HCO-cotransport. Using a double barrel microelectrode, Cemerikic et al (49) have shown that potassium deficiency induces hyperpolarization of the basolateral membrane of proximal tubule cells. Therefore, it is possible that changes in membrane potential induced by potassium depletion could be responsible for the increased activity of the Na+:CO3 :HCO-cotransporter observed in our studies.…”

Section: Resultsmentioning

confidence: 99%

Potassium depletion increases luminal Na+/H+ exchange and basolateral Na+:CO3=:HCO3- cotransport in rat renal cortex.

Soleimani

Bergman²,

Hosford³

et al. 1990

IntroductionMost HCO3 reabsorption in proximal tubules occurs via electroneutral Na+/H+ exchange in brush border membranes (BBMS) and electrogenic Na+:CO :HCO-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+J (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 (pHi 7.5, pHi 6.0, 10% C02, 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 K. of 8.2 mM in KD vs. 7.6 mM in C and V.,. of 278 nmol/min/mg protein in KD vs. 177 nmol/min/mg protein in C. Influx of 1 mM 22Na' at 5 s (pH.7.5, pH, 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 of6.2 mM in KD vs. 7.1 mM in C and V., of 209 nmol/min/mg protein in KD vs. 144 nmol/min/mg protein in C. Uptakes of Na+-dependent 13Hjglucose into BBM and I'4Cisuccinate into BLM vesicles were not different in KD and C groups, suggesting that the Na+/H+ exchanger and Na+:CO :HCO3 cotransporter activities were specifically altered in KD. We conclude that adaptive increases in basolateral Na+:CO :HCO3 cotransport and luminal Na+/H+ exchange are likely responsible for increased HCO3 reabsorption in proximal tubules of KD animals. (J. Clin. Invest. 1990.