PubMed Health⌕ Search

Biomedical subjects

H Mairbäurl

Publications and source records attributed to H Mairbäurl.

At least 19 recordsLinked to original sources
PubMed2006

Platelet count and function at high altitude and in high-altitude pulmonary edema.

Platelet aggregation is the key process in primary hemostasis. Certain conditions such as hypoxia may induce platelet aggregation and lead to platelet sequestration primarily in the pulmonary microcirculation. We investigated the influence of high-altitude exposure on platelet function as part of a larger study on 30 subjects with a history of high-altitude pulmonary edema (HAPE) and 10 healthy controls. All participants were studied in the evening and the next morning at low altitude (450 m) and after an ascent to high altitude (4,559 m). Platelet count, platelet aggregation (platelet function analyzer PFA100; using epinephrine and ADP as activators), plasma soluble P (sP)-selectin, and the coagulation parameters prothrombin fragments 1+2 and thrombin-antithrombin complex were measured. High-altitude exposure decreased the platelet count, shortened the platelet function analyzer closure time by approximately 20%, indicating increased platelet aggregation, increased sP-selectin levels to approximately 250%, but left plasma coagulation unaffected. The HAPE-susceptible subjects were prophylactically treated with either tadalafil (a phosphodiesterase 5 inhibitor), dexamethasone, or placebo in a double-blind way. Subgroup analyses between these different treatments and comparisons of the seven placebo-treated individuals developing HAPE and controls revealed no differences in platelet count, platelet aggregation, or sP-selectin values. We conclude that exposure to high altitude activates platelets, which leads to platelet aggregation, platelet consumption, and decreased platelet count. These effects are, however, not more pronounced in individuals with a history of HAPE or actually suffering from HAPE than in controls and therefore may not be a pathophysiological mechanism of HAPE.

Adult↗
PubMed2006

Hypoxia causes permeability oedema in the constant-pressure perfused rat lung.

Alveolar hypoxia causes pulmonary oedema associated with increased lung capillary pressure and decreased alveolar fluid reabsorption. However, the role of altered permeability is unclear. The aim of the present study was to test whether hypoxia affects alveolar permeability and induces pulmonary oedema in rat lungs, and whether terbutaline affects oedema formation. Isolated lungs of normoxic rats were perfused at a constant pressure (12 cmH2O) and exposed to different levels of oxygenation (1.5-35% O2). Terbutaline (10-5 M) was applied as an aerosol or with the perfusate. Online measurements indicate an earlier onset of weight gain with an increasing degree of hypoxia and a shortened lung survival time (35% O2: approximately 220 min; 1.5% O2: approximately 120 min). Terbutaline did not prevent oedema formation in hypoxic lungs. The terbutaline-induced formation of cyclic adenosine monophosphate was decreased by 50% in hypoxia (1.5% O2). In experiments terminated after 75 min, bronchoalveolar lavage fluid of hypoxic lungs contained protein that originated from perfusate indicating alveolar leakage. Since lactate dehydrogenase in perfusate was not increased at the onset of oedema formation, cell damage does not explain the increased permeability. In conclusion, these results indicate the formation of a leak for macromolecules of the isolated perfused rat lung, which is accelerated by hypoxia and causes alveolar flooding even at low perfusion pressure at a rate that exceeds absorption even after stimulation with terbutaline.

Animals↗
PubMed2003

[Acute mountain sickness and high-altitude pulmonary edema. How to protect the mountain climber from the effects of the "altitude haze"].

Acute mountain sickness (AMS) usually occurs after 6-12 hours of acute exposure to altitudes above 2,500 m. If there is no further altitude gain, it normally resolves spontaneously within a day or two. However, it may, in rare cases, progress to life-threatening cerebral edema. High-altitude pulmonary edema (HAPE) is a non-cardiogenic edema that is often preceded by symptoms of AMS. The major preventive measure is slow ascent. Acetazolamide and dexamethasone are effective in preventing AMS, while nifedipine is effective only against HAPE. Immediate descent and/or the administration of oxygen is the treatment of choice for both conditions. If this is not possible, dexamethasone may be given for severe AMS and nifedipine for HAPE.

Acetazolamide↗
PubMed2001

Hypoxia-effects on Ca(i)-signaling and ion transport activity of lung alveolar epithelial cells.

In excitatory cells specific responses upon changes in PO(2) are mediated by changes in intracellular Ca (Ca(i)). We wanted to know whether ion transport of lung alveolar epithelial cells is regulated by Ca(i) and whether Ca(i) and Ca(i) -signaling are affected by hypoxia in a way that might explain hypoxic transport inhibition (Mairbäurl et al. AJP 273: L797, 1997). The activity of transport (Na/K-pump, Na/K/2Cl-cotransport) was measured as unidirectional (86)Rb-uptake after A549 cells were exposed to hypoxia (3% O(2)). Ca(i) of primary cultured rat alveolar type II cells was measured by fura-2 epifluorescence. Depletion of Ca(i) by extracellular chelators in presence of ionomycin or with thapsigargin as well as PKC inhibition decreases (86)Rb-uptake of normoxic and hypoxic A549 cells, whereas an increased Ca(i) activates transport. Neither immediate nor prolonged exposure to hypoxia changes Ca(i) significantly. The increase in Ca(i) upon stimulation with ATP, which is caused mainly by release from intracellular stores, is smaller in hypoxia than in normoxia. These results indicate that ion transport of alveolar epithelial cells is modulated by Ca(i). A change in Ca(i) does not mediate hypoxic transport inhibition. The decreased Ca(i) transients in hypoxia might indicate a blunted response to extracellular stimuli.

Adenosine Triphosphate↗
PubMed2000

Cation transport and cell volume changes in maturing rat reticulocytes.

During maturation, reticulocytes lose membrane material, including transporters, and this is accompanied by a loss of cell water and volume. Here we determined a possible role of ion transport in adjusting cell volume during maturation. Reticulocytes and red blood cells of different ages were prepared from erythropoietin-treated rats by density gradient fractionation. Cell volume and ion transport were measured in freshly prepared cells and in reticulocytes during in vitro maturation. Reticulocytes had an increased K content and cell volume, whereas intracellular Na was decreased. All parameters approached whole blood values after 2 days in culture. Na-K pump was elevated in reticulocytes and decreased during maturation. Na-K-2Cl cotransport (NKCC) activity was lower in reticulocytes and was activated 8- and 20-fold by shrinkage and okadaic acid, respectively, whereas stimulation was barely detectable in high-buoyant density red blood cells. The ouabain- and bumetanide-insensitive Na flux in reticulocytes decreased on maturation. Most of it was inhibited by amiloride, indicating the presence of Na/proton exchange. Our results show that, although the Na-K-pump activity in reticulocytes is very much increased, the enhanced capacity of NKCC is essentially cryptic until stimulated. Both types of capacities (activities) decrease during maturation, indicating a possible loss of transport protein. The decrease was constrained to the period of reticulocyte maturation. Loss of transport capacity appears to exceed the loss of membrane surface area. Reticulocyte age-related changes in the net electrochemical driving force indicate that the increasing NKCC activity might contribute to the reduction in cell water.

Animals↗
PubMed2000

Possible role of ROS as mediators of hypoxia-induced ion transport inhibition of alveolar epithelial cells.

In oxygen-sensitive excitable cells, responses to hypoxia are initiated by membrane depolarization due to closing of the K channels that is thought to be mediated by a decrease in reactive oxygen species (ROS). Because the mechanisms of hypoxic inhibition of ion transport of alveolar epithelial cells (Planes C, Friedlander G, Loiseau A, Amiel C, and Clerici C. Am J Physiol Lung Cell Mol Physiol 271: L70-L78, 1996; Mairbäurl H, Wodopia R, Eckes S, Schulz S, and Bärtsch P. Am J Physiol Lung Cell Mol Physiol 273: L797-L806, 1997) are not yet understood, we tested the possible involvement of a hypoxia-induced change in ROS that might control transport activity. Transport was measured as (86)Rb and (22)Na uptake in A549 cells exposed to normoxia, hyperoxia, or hypoxia together with ROS donors and scavengers. H(2)O(2) < 1 mM did not affect transport, whereas 1 mM H(2)O(2) activated (22)Na uptake (+200%) but inhibited (86)Rb uptake (-30%). Also hyperoxia, aminotriazole plus menadione, and diethyldithiocarbamate inhibited (86)Rb uptake. N-acetyl-L-cysteine, diphenyleneiodonium, and tetramethylpiperidine-N-oxyl, used to reduce ROS, inhibited (86)Rb uptake, thus mimicking the hypoxic effects, whereas deferoxamine, superoxide dismutase, and catalase were ineffective. Also, hypoxic effects on ion transport were not prevented in the presence of H(2)O(2), diethyldithiocarbamate, and N-acetyl-L-cysteine. These results indicate that ion transport of A549 cells is significantly affected by decreasing or increasing cellular ROS levels and that it is possible that certain species of ROS might mediate the hypoxic effects on ion transport of alveolar epithelial cells.

Acetylcysteine↗
PubMed2000

Hypoxia decreases proteins involved in epithelial electrolyte transport in A549 cells and rat lung.

Fluid reabsorption from alveolar space is driven by active Na reabsorption via epithelial Na channels (ENaCs) and Na-K-ATPase. Both are inhibited by hypoxia. Here we tested whether hypoxia decreases Na transport by decreasing the number of copies of transporters in alveolar epithelial cells and in lungs of hypoxic rats. Membrane fractions were prepared from A549 cells exposed to hypoxia (3% O(2)) as well as from whole lung tissue and alveolar type II cells from rats exposed to hypoxia. Transport proteins were measured by Western blot analysis. In A549 cells, alpha(1)- and beta(1)-Na-K-ATPase, Na/K/2Cl cotransport, and ENaC proteins decreased during hypoxia. In whole lung tissue, alpha(1)-Na-K-ATPase and Na/K/2Cl cotransport decreased. alpha- and beta-ENaC mRNAs also decreased in hypoxic lungs. Similar results were seen in alveolar type II cells from hypoxic rats. These results indicate a slow decrease in the amount of Na-transporting proteins in alveolar epithelial cells during exposure to hypoxia that also occurs in vivo in lungs from hypoxic animals. The reduced number of transporters might account for the decreased transport activity and impaired edema clearance in hypoxic lungs.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1999

Effects of iron supplementation on total body hemoglobin during endurance training at moderate altitude.

The aim of the study was to test the hypothesis that iron supplementation in well-trained non-iron-depleted athletes leads to an enhanced increase of total body hemoglobin (TBH) during training at moderate altitude. Therefore, the members of the national German boxing team were randomly assigned to treatment with ferrous-glycine-sulfate (1335 mg equivalent to 200mg elementary iron daily) or with placebo during 18 days of endurance training at moderate altitude (1800 m). Before and after altitude training TBH was determined by CO-rebreathing, measures of exercise performance were determined with an incremental treadmill test. Before, during and after the stay at moderate altitude erythropoietin (Epo), reticulocytes (Retics) and parameters of iron metabolism were measured in venous blood. The results show that TBH did not change significantly in the placebo-group and even slightly, but significantly decreased in the iron-treated group. However, there was a significant increase of Epo and Retics in both groups during training at moderate altitude whereas parameters of iron metabolism remained unchanged. VO2max did not change either. To test whether a training-induced hemolysis, an increased urinary iron excretion or gastrointestinal blood loss could explain the unexpected drop of TBH we tested most of the boxers again during a similar training camp at low altitude (400-1000 m) to obtain measures of hemolysis, urinary iron excretion and occult hemoglobin loss with the stools. Although there were signs of an increased erythrocyte turnover no iron loss could be observed. We conclude that 18 days of endurance training at an altitude of 1800 m does not lead to an increase of TBH in non-iron-depleted athletes with and without iron supplementation.

Adult↗
PubMed1998

Lack of effect of oral Mg-supplementation on Mg in serum, blood cells, and calf muscle.

UNLABELLED: Magnesium (Mg) is important for regulating ion transport and cellular metabolism in all body tissues. In skeletal muscle Mg is involved in the neuromuscular activity, excitation, and muscle contraction. Mg deficiency can cause muscle weakness and muscle cramps. Less than 1% of total body Mg is found in serum, yet the serum Mg concentration is used to assess the body's Mg status. PURPOSE: The purpose of this study was to determine whether an oral Mg supplementation (500 mg Mg-oxide.d-1 for 3 wk) affects exercise performance, clinical symptoms, and the Mg concentration in various body compartments in athletes with low-normal serum Mg levels (N = 10 in each group). METHODS: In a double-blind, placebo-controlled study, correlation analysis between the Mg concentration in serum, blood cells, and skeletal muscle was performed to establish a measure for muscle cell Mg. RESULTS: The data indicate that a 3-wk Mg supplementation did not affect exercise performance, neuromuscular activity, or muscle related symptoms. Also, the supplementation did not increase the Mg concentration in serum or any cellular compartment studied. However, in the placebo group the renal Mg clearance decreased, whereas it increased in the subjects receiving Mg supplementation. Correlation analysis revealed that serum Mg only correlated with red cell Mg and that only leukocyte Mg correlated with the nuclear magnetic resonance (NMR)-measured muscle cell Mg concentration. CONCLUSIONS: These results indicate that Mg supplementation in athletes with low-normal serum Mg did not improve performance and failed to increase the body's Mg stores. Serum Mg appears to be a poor indicator for Mg in skeletal muscle or most other cellular compartments, but the concentration of Mg in mononuclear leukocytes might be used as an indicator of skeletal muscle Mg when NMR is not available.

Administration, Oral↗
PubMed1998

Red blood cells do not contribute to removal of K+ released from exhaustively working forearm muscle.

K+ released from exercising muscle via K+ channels needs to be removed from the interstitium into the blood to maintain high muscle cell membrane potential and allow normal muscle contractility. Uptake by red blood cells has been discussed as one mechanism that would also serve to regulate red blood cell volume, which was found to be constant despite increased plasma osmolality and K+ concentration ([K+pl]). We evaluated exercise-related changes in [K+pl], pH, osmolality, mean cellular Hb concentration, cell water, and red blood cell K+ concentration during exhaustive handgrip exercise. Unidirectional 86Rb+ (K+) uptake by red blood cells was measured in media with elevated extracellular K+, osmolarity, and catecholamines to simulate particularly those exercise-related changes in plasma composition that are known to stimulate K+ uptake. During exercise [K+pl] increased from 4.4 +/- 0.7 to 7.1 +/- 0.5 mmol/l plasma water and red blood cell K+ concentration increased from 137.2 +/- 6.0 to 144.6 +/- 4.6 mmol/l cell water (P </= 0.05), but the intracellular K+-to-mean cellular Hb concentration ratio did not change. 86Rb+ uptake by red blood cells was increased by approximately 20% on stimulation, caused by activation of the Na+-K+ pump and Na+-K+-2Cl- cotransport. Results indicate the K+ content of red blood cells did not change as cells passed the exhaustively exercising forearm muscle despite the elevated [K+pl]. The tendency for an increase in intracellular K+ concentration was due to a slight, although statistically not significant, decrease in red blood cell volume. K+ uptake, although elevated, was too small to move significant amounts of K+ into red blood cells. Our results suggest that red blood cells do not contribute to the removal of K+ released from muscle and do not regulate their volume by K+ uptake during exhaustive forearm exercise.

Adult↗
PubMed1998

[Pseudo-anemia caused by sports].

Regular physical training leads to an increase of plasma volume by 10-20 percent. Therefore, hemoglobin concentration slightly below normal values in the presence of low-normal serum ferritin levels in athletes are usually due to a dilutional "pseudoanemia". Several cross sectional studies indicate that true iron deficiency anemia is not more frequent in athletes than in the general population. Since regular physical activity, especially extensive, running increases iron loss, mild iron deficiency (abnormal serum ferritin and normal hemoglobin concentration) and sometimes true iron deficiency anemia can occur especially when nutritional iron intake is insufficient and iron demand is increased because of growth (children, adolescents) or additional iron loss (menstruation). Several controlled studies indicate that iron supplementation (recommended dose 2 x 100 mg elementary iron/day) improves performance only when hemoglobin concentration increases, i.e. when iron deficiency anemia is present. On the contrary, iron supplementation has no measurable effects on performance when hemoglobin concentration cannot be increased, i.e. in mild iron deficiency.

Adolescent↗
PubMed1997

Impairment of cation transport in A549 cells and rat alveolar epithelial cells by hypoxia.

A reduced cation reabsorption across the alveolar epithelium decreases water reabsorption from the alveoli and could diminish clearing accumulated fluid. To test whether hypoxia restricts cation transport in alveolar epithelial cells, cation uptake was measured in rat lung alveolar type II pneumocytes (AII cells) in primary culture and in A549 cells exposed to normoxia and hypoxia. In AII and A549 cells, hypoxia caused a PO2-dependent inhibition of the Na-K pump, of Na-K-2Cl cotransport, and of total and amiloride-sensitive 22Na uptake. Nifedipine failed to prevent hypoxia-induced transport inhibition in both cell types. In A549 cells, the inhibition of the Na-K pump and Na-K-2Cl cotransport occurred within approximately 30 min of hypoxia, was stable >20 h, and was reversed by 2 h of reoxygenation. There was also a reduction in cell membrane-associated Na-K-ATPase and a decrease in Na-K-2Cl cotransport flux after full activation with calyculin A, indicating a decreased transport capacity. [14C]serine incorporation into cell proteins was reduced in hypoxic A549 cells, but inhibition of protein synthesis with cycloheximide did not reduce ion transport. In AII and A549 cells, ATP levels decreased slightly, and ADP and the ATP-to-ADP ratio were unchanged after 4 h of hypoxia. In A549 cells, lactate, intracellular Na, and intracellular K were unchanged. These results indicate that hypoxia inhibits apical Na entry pathways and the basolateral Na-K pump in A549 cells and rat AII pneumocytes in culture, indicating a hypoxia-induced reduction of transepithelial Na transport and water reabsorption by alveolar epithelium. If similar changes occur in vivo, the impaired cation transport across alveolar epithelial cells might contribute to the formation of hypoxic pulmonary edema.

Adenosine Diphosphate↗
PubMed1996

Na(+)-K(+)-2Cl- cotransport, Na+/H+ exchange, and cell volume in ferret erythrocytes.

Ferrets have high-Na+ and low-K+ erythrocytes (113 and 5.4 mmol/l cell water) due to the lack of Na(+)-K+ pumps. Because ferret erythrocytes have a high capacity for Na(+)-K(+)-2Cl- cotransport, the present study was undertaken to evaluate cell volume-related changes in cotransport activity and its role in volume regulation. With cell shrinkage, Na(+)-K(+)-2Cl- cotransport is activated about twofold. A large bumetanide-insensitive Na+ uptake component that has not yet been described is found in shrunken erythrocytes. Its inhibition by amiloride (concn inhibiting 50% of maximal response = 12 microM) and the Na+ dependence of amiloride-sensitive extracellular pH changes measured in cells suspended in hypertonic unbuffered medium indicate that this flux represents Na+/H+ exchange. Shrinkage activation of both transporters follows a time lag of approximately 3 min and also requires normal levels of ATP. ATP depletion inhibits Na(+)-K(+)-2Cl- cotransport even at normal cell volume. Both transporters are partially inhibited by the protein kinase inhibitors staurosporine and K252a, and activators of protein kinases A and C do not affect transport. Okadaic acid inhibition of protein phosphatases activates Na(+)-K(+)-2Cl- cotransport to its maximal activity (same after shrinkage), but shrinkage and okadaic acid activation are not additive. In contrast, okadaic acid activates Na+/H+ exchange even in shrunken cells. These results indicate that cell shrinkage activates Na(+)-K(+)-2Cl- cotransport and Na+/H+ exchange probably by phosphorylation processes.

Adenosine Triphosphate↗
PubMed1994

Red blood cell function in hypoxia at altitude and exercise.

Oxygen transport by red blood cells is regulated by erythropoiesis and Hb-O2-affinity. The O2 carrying capacity is characterized by changes in hematocrit, red blood count or the mass of circulating red blood cells. Erythropoiesis is controlled by the hormone erythropoietin, which induces slow changes of the O2-transport capacity. The Hb-O2-affinity is modified mainly by pH and 2,3-DPG. Despite their apparently diverse effects e.g. in hypoxia at high altitude, a compromise seems to be adopted optimizing both arterial O2-loading and peripheral O2-unloading. In contrast to erythropoiesis, adjustments of the Hb-O2-affinity occur fast and allow rapid adjustments of O2-binding and release. In the intact organism the significance of changes in Hb-O2-affinity for tissue oxygen supply relative to adjustments of cardiac output, microcirculation and O2-transport capacity is not completely understood yet, but beneficial effects were demonstrated in isolated organs. It is, however, the least energy-demanding way of optimizing tissue O2-supply, which might be of significance in extreme situations. In severe hypoxia adjustments of both, hematocrit and Hb-O2-affinity, are insufficient to maintain tissue O2-supply. Alterations of Hb-O2-affinity are also insufficient to compensate for severe anemia.

Altitude↗
PubMed1993

Interactions between Hb, Mg, DPG, ATP, and Cl determine the change in Hb-O2 affinity at high altitude.

Ascent to high altitude (HA) causes an increase in erythrocyte 2,3-diphsophoglycerate (DPG) and standard PO2 at 50% O2 saturation, PCO2 40 Torr, and blood pH 7.4 (P50,st). We studied the early phase of acclimatization to HA of mountaineers without and with a history of HA pulmonary edema. Tests were performed before ascent and after arrival at HA (4,559 m), approximately 22 h after the departure from low altitude (HA1) and on the following 3 days at HA (HA2-HA4). We investigated the relation between changes in DPG and P50,st, since at moderate altitude P50,st increases more rapidly than DPG, indicating that other factors may contribute to the change in P50,st. Combined effects of interaction between allosteric effectors of hemoglobin (Hb) (DPG, ATP, Cl) and Mg, which competes with Hb for DPG and ATP binding, might explain that phenomenon. Therefore concentrations of liganded Hb species were calculated from the total erythrocyte concentrations of the ligands by use of published binding constants and were related to changes in Hb-O2 affinity. P50,st increased at HA by approximately 4.5 Torr; the concentration of total DPG and ATP increased by 28 and 19%, respectively. Whereas P50,st reached a plateau already at HA1, the concentration of DPG reached its highest value at HA4. The erythrocyte Cl concentration decreased, whereas cellular Hb and Mg concentrations increased slightly. The sum of concentrations of all liganded Hb species increased, reaching 79% of its total change within 22 h after ascent; this can mainly be attributed to the change in the concentration of Hb[DPG] (+77% of total increase).(ABSTRACT TRUNCATED AT 250 WORDS)

2,3-Diphosphoglycerate↗
PubMed1992

Internal magnesium, 2,3-diphosphoglycerate, and the regulation of the steady-state volume of human red blood cells by the Na/K/2Cl cotransport system.

This study is concerned with the relationship between the Na/K/Cl cotransport system and the steady-state volume (MCV) of red blood cells. Cotransport rate was determined in unfractionated and density-separated red cells of different MCV from different donors to see whether cotransport differences contribute to the difference in the distribution of MCVs. Cotransport, studied in cells at their original MCVs, was determined as the bumetanide (10 microM)-sensitive 22Na efflux in the presence of ouabain (50 microM) after adjusting cellular Na (Nai) and Ki to achieve near maximal transport rates. This condition was chosen to rule out MCV-related differences in Nai and Ki that might contribute to differences in the net chemical driving force for cotransport. We found that in both unfractionated and density-separated red cells the cotransport rate was inversely correlated with MCV. MCV was correlated directly with red cell 2,3-diphosphoglycerate (DPG), whereas total red cell Mg was only slightly elevated in cells with high MCV. Thus intracellular free Mg (Mgifree) is evidently lower in red cells with high 2,3-DPG (i.e., high MCV) and vice versa. Results from flux measurements at their original MCVs, after altering Mgifree with the ionophore A23187, indicated a high Mgi sensitivity of cotransport: depletion of Mgifree inhibited and an elevation of Mgifree increased the cotransport rate. The apparent K0.5 for Mgifree was approximately 0.4 mM. Maximizing Mgifree at optimum Nai and Ki minimized the differences in cotransport rates among the different donors. It is concluded that the relative cotransport rate is regulated for cells in the steady state at their original cell volume, not by the number of copies of the cotransporter but by differences in Mgifree. The interindividual differences in Mgifree, determined primarily by differences in the 2,3-DPG content, are responsible for the differences in the relative cotransport activity that results in an inverse relationship with in vivo differences in MCV. Indirect evidence indicates that the relative cotransport rate, as indexed by Mgifree, is determined by the phosphorylated level of the cotransport system.

2,3-Diphosphoglycerate↗
PubMed1991

Relationship between sodium transport and intracellular ATP in isolated perfused rabbit proximal convoluted tubule.

The effect of alterations in sodium transport on cell ATP content and pH in the isolated perfused proximal convoluted tubule (PCT) of the rabbit was examined. Stimulating sodium transport by the addition of luminal glucose and alanine decreased cell ATP from 4.44 +/- 0.93 to 2.69 +/- 0.62 mM (n = 4), increased intracellular pH by 0.13 +/- 0.02 (n = 7), and increased cell volume by 0.10 +/- 0.02 nl/mm (n = 4). Blocking the sodium pump with 10(-4) M strophanthidin in tubules in which sodium transport had been stimulated increased cell ATP from 2.04 +/- 0.24 to 2.42 +/- 0.32 mM (n = 6). In parallel experiments the same dose of strophanthidin depolarized the basolateral membrane from -52.6 +/- 1.9 to -6.4 +/- 1.6 mV, depolarized the transepithelial potential from -3.2 +/- 0.3 to -0.1 +/- 0.1 mV, and reduced the basolateral membrane potassium transference number from 0.47 to 0.26 indicating a reduction in basolateral potassium conductance. Since strophanthidin caused a cell alkalinization of 0.15 +/- 0.03, this latter effect cannot be due to changes of intracellular pH. Strophanthidin caused no change in cell volume over the period studied, suggesting that stretch-activated potassium channels are not involved either. Instead, potassium conductance inhibition may be the result of the closure of ATP-sensitive potassium channels. These same channels might thus be partly responsible for the increase in potassium conductance commonly observed during stimulation of sodium transport.

Adenosine Triphosphate↗