Effects of prostaglandin E2 on excretion and reabsorption of sodium and fluid in rat kidneys (micropuncture studies)

Summary The effects of i.v. infusions of Prostaglandin E₂ on renal excretion of sodium and fluid were investigated in rats. Increasing diuresis was observed at infusion rates from 10 to 100 ng/min·100 g BW. Higher rates depressed the arterial blood pressure and urinary excretion rates. At 100 ng PGE₂/min·100 g BW urinary flow rate increased approximately 3 times and sodium excretion approximately 8–10 times above the control level. The urine/plasma concentration ratio of Na averaged 1.7 compared with 0.5 in controls. Potassium excretion, however, was only slightly enhanced.The effects on sodium and fluid excretion were not correlated with changes of total kidney GFR. Single nephron GFR of superficial nephrons remained unchanged during the PGE₂ infusion.Fractional proximal reabsorption of sodium and fluid, calculated from endproximal tubular fluid/plasma concentration ratios of Na and Inulin, were not inflenced by PGE₂. Transtubular net movements, calculated from split drop half time, were not significantly affected, too. Tubular transit time, however, was shortened, and fractional proximal reabsorption was decreased, when calculated fromt1/2 andT. This, too, indicates thatt1/2 andT do not always sufficiently define the fractional reabsorption.The normal decrease of the TF/P ratio of Na along the distal convolution is reduced under the influence of PGE₂. Approximately 2% of the filtered Na remain unreabsorbed in the distal convolution in addition to the amount found in controls. The high Na concentration in the final urine is established in the collecting ducts by an ADH like action.Preliminary reports of the results were presented in part at the 33rd meeting of the Deutsche Pharmakologische Gesellschaft in Heidelberg 1970.     

Oxygen diffusivity in tumor tissue (DS-Carcinosarcoma) under temperature conditions within the range of 20–40°C

Summary The O₂ diffusion constants D and K of tumor tissue (DS-Carcinosarcoma in the rat kidney) were determined at temperatures of 20, 30, 37, and 40°C. The following mean values were obtained for the conditions of 37°C: D=1.75·10^–5 cm²/s and K=1.9·10^–5 mlO₂/cm·min·atm. Within the range of 20–40°C, temperature variations in tumor tissue cause changes in the O₂ diffusion coefficient D of 2.0–2.5%/°C and in the Krogh O₂ diffusion constant K of 0.5–1.5%/°C. The measured O₂ diffusion constants for tumor tissue correspond to values of normal tissue with similar water content. This indicates that the insufficient O₂ supply in DS-Carcinosarcoma is due not to unfavorable O₂ diffusivity of the tumor tissue but rather to a decreased convective O₂ transport and to insufficient capillarization. An analysis of O₂ diffusion in DS-Carcinosarcoma tissue using the determined O₂ diffusion constants lead to the result that, under the conditions of arterial normoxia and normocapnia, critical O₂ supply conditions are to be expected when the intercapillary distance exceeds approximately 120 m.     

The diffusion coefficient of myoglobin in muscle homogenate

Summary One layer of muscle homogenate rich in myoglobin (heart muscle of the rat) and three layers of muscle homogenate poor in myoglobin (skeletal muscle of the rat) were arranged one upon the other, than reseparated after a certain time. According to the concentration change of myoglobin in the layers the diffusion coefficient of myoglobin is 1.5×10^–7 cm²/sec at 20° C and 2.7×10^–7 cm²/sec at 37° C. From this result it was calculated that the facilitated O₂ diffusion on the basis of myoglobin diffusion amounts, at 37° C, to the free O₂ diffusion at about 3 mm Hg partial pressure difference when myoglobin concentration is 2×10^–7 mol (3 mg) per g wet muscle.     

Receptors for neurohypophyseal hormones along the rat nephron: 125I-labelled d(CH2)5[Tyr(Me)2, Thr4, Orn8, Tyr-NH 2 9 ] vasotocin binding in microdissected tubules

A microassay was developed to measure the binding of the labelled monoiodinated analogue [1-(mercapto-,-cyclopentamethylenepropionic acid), 2-O-mithyltyrosine, 4-threonine, 8-ornithine, 9-¹²⁵I-tyrosylamide]vasotocin ¹²⁵I-d(CH₂)₅[Tyr (Me)², Thr⁴, Tyr-NH ₂ ⁹ ]OVT to isolated nephron segments microdissected from collagenase-treated rat kidneys. When determined using 1.7 nM labelled ligand at 4° C, specific binding sites (expressed at 10^–18 mol ¹²⁵I-d(CH₂)₅[Tyr (Me)², Thr⁴, Tyr-NH ₂ ⁹ ]OVT bound/mm tubule length) were found in medullary thick ascending limbs (MTAL), 1.67±0.49; cortical thick ascending limbs, 2.20±0.80; cortical collecting ducts, 2.39±0.86; outer medullary collecting ducts (OMCD), 2.54±0.53 and inner medullary collecting ducts, 5.33±0.40, whereas no specific binding could be detected in glomeruli and proximal tubules. Specific ¹²⁵I-d(CH₂)₅[Tyr (Me)², Thr⁴, Tyr-NH ₂ ⁹ ]OVT binding to OMCD was saturable with incubation time and reversible after elimination of free labelled ligand (the association and dissociation rate constants at 4° C were 1.06×10⁷ M^–1 min^–1 and 1.95×10^–2 min^–1 respectively). The stereospecificity of MTAL and OMCD binding sites was assessed in competitive experiments revealing the following recognition pattern for a series of eight vasopressin analogues:ddAVP>AVP>d(CH₂)₅-[Tyr (Me)², Thr⁴, Tyr-NH ₂ ⁹ ]OVT=AVT=OT>d(CH₂)₅[Tyr(Me)²]AVP=[Thr⁴, Gly⁷]OT>[Phe², Orn⁸]VT, whereas pharmacological concentrations of insulin and glucagon did not impair radioligand binding. These results indicate that the detected labelled binding sites might correspond mainly to physiological V₂ vasopressin receptors.     

Bio-energetic profile in 144 boys aged from 6 to 15 years with special reference to sexual maturation

Summary The effects of growth and pubertal development on bio-energetic characteristics were studied in boys aged 6–15 years (n = 144; transverse study). Maximal oxygen consumption (VO_2max, direct method), mechanical power at (VO_2max ( ), maximal anaerobic power (P_max; force-velocity test), mean power in 30-s sprint (P _30s; Wingate test) were evaluated and the ratios between P_max,P _30s and were calculated. Sexual maturation was determined using salivary testosterone as an objective indicator. Normalized for body massVO_2max remained constant from 6 to 15 years (49 ml· min^–1 · kg^–1, SD 6), whilst P_max andP _30s increased from 6–8 to 14–15 years, from 6.2 W · kg^–1, SD 1.1 to 10.8 W · kg^–1, SD 1.4 and from 4.7 W · kg^–1, SD 1.0 to 7.6 W · kg^–1, SD 1.0, respectively, (P < 0.001). The ratio P_max: was 1.7 SD 3.0 at 6–8 years and reached 2.8 SD 0.5 at 14–15 years and the ratioP _30s: changed similarly from 1.3 SD 0.3 to 1.9 SD 0.3. In contrast, the ratio P_max:P _30s remained unchanged (1.4 SD 0.2). Significant relationships (P < 0.001) were observed between P_max (W · kg^–1),P _30s (W · kg^–1), blood lactate concentrations after the Wingate test, and age, height, mass and salivary testosterone concentration. This indicates that growth and maturation have together an important role in the development of anaerobic metabolism.     

Energetics of locomotion in African pygmies

Summary The energy cost of walking (C _w). and running (C _r), and the maximal O₂ consumption (VO_2max) were determined in a field study on 17 Pygmies (age 24 years, SD 6; height 160 cm, SD 5; body mass 57.2 kg, SD 4.8) living in the region of Bipindi, Cameroon. TheC _w varied from 112 ml·kg^–1·km^–1, SD 25 [velocity (), 4 km·h^–1] to 143 ml·kg^–1·km^–1, SD 16 (, 7 km·h^–1). Optimal walking was 5 km·h^–1. TheC _r was 156 ml·kg^–1·km^–1, SD 14 (, 10 km·h^–1) and was constant in the 8–11 km·h^–1 speed range. TheVO_2max was 33.7 ml·kg^–1· min^–1, i.e. lower than in other African populations of the same age. TheC _r andC _w were lower than in taller Caucasian endurance runners. These findings, which challenge the theory of physical similarity as applied to animal locomotion, may depend either on the mechanics of locomotion which in Pygmies may be different from that observed in Caucasians, or on a greater mechanical efficiency in Pygmies than in Caucasians. The lowC _r values observed enable Pygmies to reach higher running speeds than would be expected on the basis of theirVO_2max.     

Effect of extracellular volume expansion on renal cortical and medullary Na+−K+-ATPase

Summary The role of renal Na⁺–K⁺-ATPase in the acute changes in sodium reabsorption caused by isotonic volume expansion was evaluatedin vivo andin vitro in the rat and the dog. Duringin vivo volume expansion with isotonic saline in the rat, renal medullary Na⁺–K⁺-ATPase specific activity increased, while the simultaneously determined cortical Na⁺–K⁺-ATPase specific activity and kinetics remained unchanged. Furthermore, experimentsin vitro failed to demonstrate a circulating inhibitor of renal Na⁺–K⁺-ATPase both in plasma dialysates from volume-expanded rats and in plasma dialysates concentrated 20-fold by ultrafiltration from volume-expanded dogs. These results suggest that the decreased proximal tubular reabsorption of sodium during volume expansion is not mediated by inhibition of renal cortical Na⁺–K⁺-ATPase. The acute increment in medullary Na⁺–K⁺-ATPase observed could represent an adaptive response to increased sodium reabsorption by the loops of Henle, and raises the possibility that this enzyme may participate in relatively rapid adjustments in the transport of sodium by the renal tubule.     

Die Beeinflussung der alveolär-arteriellen O2-Druckdifferenz durch inerte Gase

Zusammenfassung Bei 10 Probanden im Alter von 20–35 Jahren wurde dieAaDO₂ während der Atmung von N₂–O₂, He–O₂- und Ar–O₂-Gemischen mit gleichem inspiratorischen Sauerstoffpartialdruck und bei Konstanz des alveolaren Kohlen-säurepartialdruckes gemessen. Den alveolaren und inspiratorischen Sauerstoff-partialdruck bestimmten wir durch fortlaufende massenspektrometrische Analyse der Atemluft (endexspiratorisch), den arteriellen Sauerstoffpartialdruck aus dem Capillarblut des hyperämisierten Ohrläppchens. DieAaDO₂ betrug im Mittel bei Atmung von N₂–O₂ 8,7 Torr, bei Atmung von He–O₂ 15,3 Torr und bei Atmung von Ar–O₂ 16,3 Torr. Statistisch sind diese Werte signifikant verschieden.Eine Beziehung zu verschiedenen physikalischen Eigenschaften der Gase und der daraus resultierenden intrapulmonalen Gasmischung oder Verteilung der Ventilation läßt sich nicht widerspruchslos herstellen. Eine Änderung von _A/Q kann nur hypothetisch erörtert werden.     

A vacuum chamber for simplifying the collection of expired air samples

Summary Metalized bags for collection and storage of expired air for the study of oxygen consumption in man have been described by Johnsonet al. [J. appl. Physiol.22, 377–379 (1967)]. We have developed a vacuum chamber to permit rapid, multiple sampling with these metalized bags. The reproducibility and reliability of oxygen and carbon dioxide measurements of samples collected with the vacuum chamber compare favorably with accepted standard techniques, such as that of Campney and Pleasants [Res. Quart. Amer. Ass. Hlth phys. Educ.36, 207–210 (1965)].     

Differential effects of ADH on sodium,chloride, potassium,calcium and magnesium transport in cortical and medullary thick ascending limbs of mouse nephron

The effect of antidiuretic hormone (arginine vasopressin, AVP) on transepithelial Na⁺, Cl^–, K⁺, Ca²⁺ and Mg²⁺ net transports was investigated in medullary (mTAL) and cortical (cTAL) segments of the thick ascending limb (TAL) of mouse nephron, perfused in vitro. Transepithelial net fluxes (J _Na ⁺,J _Cl ^–,J _K ⁺,J _Ca ²⁺,J _Mg ²⁺) were determined by electron probe analysis of the collected tubular fluid. Transepithelial potential difference (PD_te) and transepithelial resistance (R_te) were measured simultaneously. cTAL segments were bathed and perfused with isoosmolal, HCO ₃ ^– containing Ringer solutions, mTAL segments were bathed and perfused with isoosmolal HCO ₃ ^– free Ringer solutions. In cTAL segments, AVP (10^–10 mol·l^–1) significantly increasedJ _Mg ²⁺ andJ _Ca ²⁺ from 0.39±0.08 to 0.58±0.10 and from 0.86±0.13 to 1.19±0.15 pmol·min^–1 mm^–1 respectively. NeitherJ _Na ⁺ norJ _Cl ^–, (J _Na ⁺: 213±30 versus 221±28 pmol·min^–1 mm^–1,J _Cl ^–: 206±30 versus 220±23 pmol·min^–1 mm^–1) nor PD_te (13.4±1.3 mV versus 14.1±1.9 mV) or R_te (24.6±6.5 cm² versus 22.6±6.4 cm²) were significantly changed by AVP. No significant effect of AVP on net K⁺ transport was observed. In mTAL segments, Mg²⁺ and Ca²⁺ net transports were close to zero and AVP (10^–10 mol·l^–1) elicited no effect. However NaCl net reabsorption was significantly stimulated by the hormone,J _Na ⁺ increased from 107±33 to 148±30 andJ _Cl ^– from 121±33 to 165±32 pmol·min^–1 mm^–1. The rise inJ _NaCl was accompanied by an increase in PD_te from 9.0±0.7 to 13.5±0.9 mV and a decrease in R_te from 14.4±2.0 to 11.2±1.7 cm². No K⁺ net transport was detected, either under control conditions or in the presence of AVP.To test for a possible effect of HCO ₃ ^– on transepithelial ion fluxes, mTAL segments were bathed and perfused with HCO ₃ ^– containing Ringer solutions. With the exception ofJ _Ca ²⁺ which was significantly different from zero (J _Ca ²⁺: 0.26±0.06 pmol·min^–1 mm^–1), net transepithelial fluxes of Na⁺, Cl^–, K⁺ and Mg²⁺ were unaffected by HCO ₃ ^– . In the presence of AVP,J _Mg ²⁺ andJ _Ca ²⁺ were unaltered whereasJ _NaCl was stimulated to the same extent as observed in the absence of HCO ₃ ^– . In conclusion our results indicate heterogeneity of response to AVP in cortical and medullary segments of the TAL segment, since AVP stimulates Ca²⁺ and Mg²⁺ reabsorption in the cortical part and Na⁺ and Cl^– reabsorption in the medullary part of this nephron segment.This study was supported by the Commission des communautés européennes, grant no. ST2J 00951 F(CD), and by Wissenschafts-ausschuß der Nato über den DAAD     

Does the threshold of transcutaneous partial pressure of carbon dioxide represent the respiratory compensation point or anaerobic threshold?

On reaching the respiratory compensation point (RCP) during rapidly increasing incremental exercise, the ratio of minute ventilation (V_E) to CO₂ output (VCO₂) rises, which coincides with changes of arterial partial pressure of carbon dioxide (P _aCO₂). Since P _aCO₂ changes can be monitored by transcutaneous partial pressure of carbon dioxide (PCO_2,tc) RCP may be estimated by PCO_2,tc measurement. Few available studies, however, have dealt with comparisons between PCO_2,tc threshold (T _AT) and lactic, ventilatory or gas exchange threshold (V _AT), and the results have been conflicting. This study was designed to examine whether this threshold represents RCP rather than V _AT. A group of 11 male athletes performed incremental excercise (25 W · min^–1) on a cycle ergometer. The PCO_2,tc at (44°C) was continuously measured. Gas exchange was computed breath-by-breath, and hyperaemized capillary blood for lactate concentration ([la^–]_b) and P _aCO₂ measurements was sampled each 2 min. The T _AT was determined at the deflection point of PCO_2,tc curve where PCO_2,tc began to decrease continuously. The V _AT and RCP were evaluated with VCO₂ compared with oxygen uptake (VO₂) and V_E compared with the VCO₂ method, respectively. The PCO_2,tc correlated with P _aCO₂ and end-tidal PCO₂. At T _AT, power output [P, 294 (SD 40) W], VO₂ [4.18 (SD 0.57)l · min^–1] and [la^–] [4.40 (SD 0.64) mmol · l^–1] were significantly higher than those at V _AT[P 242 (SD 26) W, VO₂ 3.56 (SD 0.53) l · min^–1 and [la^–]_b 3.52 (SD 0.75), mmol · l^–1 respectively], but close to those at RCP [P 289 (SD 37) W; VO₂ 3.97 (SD 0.43) l · min^– and [la^–]_b 4.19 (SD 0.62) mmol · l^–1, respectively]. Accordingly, linear correlation and regression analyses showed that P, VO₂ and [la^–]_b at T _AT were closer to those at RCP than at V _AT. In conclusion, the T _AT reflected the RCP rather than V _AT during rapidly increasing incremental exercise.     

[Arginine]vasopressin hydrolyses phosphoinositides in the medullary thick ascending limb of mouse nephron

NaCl reabsorption across the thick ascending limb of Henle's loop (TAL) is stimulated by several hormones, in particular vasopressin acting through V₂ receptors and cyclic AMP production. This study used suspensions of medullary TAL (mTAL) tubules from the mouse nephron to investigate the possibility that, besides activating adenylyl cyclase, vasopressin also stimulates phospholipase C via V₁ receptor occupancy. Two different methods, phosphoinositide labelling and inositol trisphosphate (InsP ₃) radioimmunoassay, were used to show that [arginine]vasopressin (AVP) rapidly stimulated the formation of InsP ₃, which peaked at 200%–250% of control within the first minute of incubation with 10 nmol/l vasopressin at 37°C, and declined to basal level after 5–10 min. Dose/response curves for InsP ₃, established at 30°C and 37° C using radioimmunoassay, showed a half-maximal stimulation of InsP ₃ production at about 1 nmol/l AVP and a maximal response at 10 nmol/l. Similar values were obtained for the response to AVP in terms of cAMP accumulation. InsP ₃ content in the presence of higher concentrations of AVP (1 mol/l) was significantly lower (P<0.001) than in the presence of 10 nmol/l AVP, giving a bell-shaped appearance to the dose/response curve at 37° C but not at 30° C. The V₂ receptor agonist, 1-deamino-[8DArg]vasopressin (dAVP) did not stimulate the formation of InsP ₃, and the V₁ receptor antagonist d(CH₂)₅[Tyr(Me)²]AVP inhibited AVP-induced InsP ₃ formation, which therefore appeared to be mediated by V₁ receptor occupancy. Under the same conditions, AVP also induced the formation of diradylglycerol via V₁ receptor activation, with an analogous dose/response curve. These results show that AVP, in addition to its well-known action through V₂ receptors, also acts on the mouse mTAL through a V₁-mediated stimulation of phospholipase C. Cyclic AMP controls this transduction pathway: dAVP (10 nmol/l), dibutyryl-cAMP (1 mmol/l and 0.1 mmol/l) and forskolin (1 mol/l) decreased the InsP ₃ formation induced by AVP. Dibutyryl-cAMP itself at 37°C also reduced the diglyceride content.     

Effect of temperature on spontaneous Ca2+-activated CI− currents in rabbit portal vein cells

The effect of temperature on the time course of spontaneous transient inward (Ca²⁺-activated Cl^–) currents (STICs) was investigated with the perforated patch technique in rabbit portal vein cells. STICs decayed exponentially at temperatures between 17° C and 35° C. The time constant of the decay () was decreased with increasing temperature and had a temperature coefficient, Q ₁₀, of 2.6. The temperature sensitivity of could be described by the Arrhenius equation which gave an activation energy of 16 kcal/mol. This result indicates that STIC decay is governed by a single first-order reaction and provides further support for the hypothesis that the decay is due to the gating properties of Ca²⁺-activated Cl^– channels.     

Effects of glucagon on Na+, Cl−, K+, Mg2+ and Ca2+ transports in cortical and medullary thick ascending limbs of mouse kidney

The effects of glucagon on transepithelial Na⁺, Cl^–, K⁺, Ca²⁺ and Mg²⁺ net fluxes were investigated in isolated perfused cortical (cTAL) and medullary (mTAL) thick ascending limbs of Henle's loop of the mouse nephron. Transepithelial ion net fluxes (J _Na ⁺,J _Cl ^–,J _K ⁺,J _Ca ²⁺,J _Mg ²⁺) were determined by electron probe analysis of the collected tubular fluid. Simultaneously the transepithelial voltage (PD_te) and the transepithelial resistance (R _te) were recorded. In cTAL-segments (n=8), glucagon (1.2×10^–8 mol · l^–1) stimulated significantly the reabsorption of Na⁺, Cl^–, Ca²⁺ and Mg²⁺J _Na ⁺ increased from 204±20 to 228±23 pmol · min^–1 · mm^–1,J _Cl ^– from 203±18 to 234±21 pmol · min^–1 · mm^–1,J _Ca ²⁺ from 0.52±0.13 to 1.34±0.30 pmol · min^–1 · mm^–1 andJ _Mg ²⁺ from 0.51±0.08 to 0.84±0.08 pmol · min^–1 · mm^–1.J _K+ remained unchanged: 3.2±1.3 versus 4.0±1.9 pmol · min^–1 · mm^–1. Neither PD_te (16.3±1.5 versus 15.9±1.4 mV) norR _te (22.5±3.0 versus 20.3±2.6 cm²) were changed significantly by glucagon. However, in the post-experimental periods a significant decrease in PD_te and increase inR _te were noted. In mTAL-segments (n=9), Mg²⁺ and Ca²⁺ transports were close to zero and glucagon elicited no significant effect. The reabsorptions of Na⁺ and Cl^–, however, were strongly stimulated:J _Na ⁺ increased from 153±17 to 226±30 pmol · min^–1 · mm^–1 andJ _Cl ^– from 151±23 to 243±30 pmol · min^–1 · mm^–1. The rise in NaCl transport was accompanied by an increase in PD_te from 10.3±1.1 to 12.3±1.2 mV and a decrease inR _te from 19.1±2.7 to 17.8±2.0 cm². No net K⁺ movement was detectable either in the absence or in the presence of glucagon. A micropuncture study carried out in hormone-deprived rats indicated that glucagon stimulates Na⁺, Cl^–, K⁺, Mg²⁺ and Ca²⁺ reabsorptions in the loop of Henle. In conclusion our data demonstrate that glucagon stimulates NaCl reabsorption in the mTAL segment and to a lesser extent in the cTAL segment whereas it stimulates Ca²⁺ and Mg²⁺ reabsorptions only in the cortical part of the thick ascending limb of the mouse nephron. These data are in good agreement with, and extend, those obtained in vivo on the rat with the hormone-deprived model.This study was supported by the Commission des Communautés Européennes, Grant no. ST 23, 00951F (CD) and by Wissenschaftsausschuß der Nato über den DAAD     

O2 consumption,aerobic glycolysis and tissue phosphagen content during activation of the NA+/K+ pump in rat portal vein

Oxygen consumption, lactate production and tissue contents of ATP, phosphocreatine (PCr) and lactate were measured following readdition of K⁺ to K⁺-depleted rat portal veins, in order to study the energy turnover associated with Na⁺/K⁺ pumping. During incubation in K⁺-free medium at 37° C spontaneous contractions disappeared in 10–20 min. Readdition of K⁺ (5.9 mM) after 40 min K⁺-free incubation caused hyperpolarization of the cell membrane for the first 5–10 min and then gradual depolarization with return of spontaneous action potentials and contractions by 10–20 min. During the first 4–6 min after K⁺ readdition aerobic lactate production was about doubled and then gradually returned to the original level (0.17 mol/min g) at about 20 min. The increase in glycolytic rate was prevented by 1 mM ouabain. In contrast, O₂ consumption (in K⁺-free medium, 0.38 mol/min g) rose by about 10% when K⁺ was added and this increase lasted about 5 min. By 8 min after K⁺ addition the increased glycolysis and oxidative phosphorylation had accounted for each about the same amount of extra ATP generation over that extrapolated from the steady rate before K⁺ addition. The average total increase in ATP turnover in the first 8 min was 15%. During this period there was no change in the cellular content of ATP, PCr, or extractable ADP. The results indicate that Na⁺/K⁺ pumping utilizes a relatively small share of the total energy turnover in the vascular smooth muscle but is to a large extent dependent on aerobic glycolysis and therefore a major site of carbohydrate usage.     

Effect of variations in blood hydrogen ion concentration on pulmonary gas exchange of artificially ventilated dogs

The effect of variation of blood hydrogen ion concentration on arterial and mixed venousP _{O 2},ideal alveolar-arterial O₂ pressure difference (P _AiO₂–P _aO₂),venous admixture (Q _s/Q _t), arterio-alveolar CO₂ pressure difference (a–A)D _{CO 2},physiological dead space to tidal volume ratio (V _D/V_T),cardiac output (Q _t) and mean pulmonary arterial pressure ( ) has been studied. Arterial and mixed venousP _{O 2}increased and (P _AiO₂–P _aO₂)decreased with increasing blood hydrogen ion concentration. No change in (Q _s/Q _t), (a–A)-D _{CO 2},V _D/V_T,Q _t and was observed.The effect of hydrogen ion concentration on arterial and mixed venousP _{O 2}and on (P _AiO₂–P _aO₂)is mainly due to a shift of the blood oxyhemoglobin dissociation curve (ODC), i.e. due to the Bohr effect. The upper part of the ODC is more flat in alkalosis (shift to the left) than in acidosis (shift to the right). Therefore the same end-capillary to arterial O₂ content difference results in a greater (P _AiO₂–P _aO₂)in alkalosis than in acidosis. Any factor influencing the slope of the upper part of the ODC is expected to affect the arterialP _{O 2}and the (P _AiO₂–P _aO₂)by this mechanism. Similarly any factor shifting the steep part of the ODC is expected to affect theP _{O 2}of the mixed venous blood.     

Temperature-induced transitory and steady-state changes in the calcium current of guinea pig ventricular myocytes

I_Ca was recorded in quinea pig ventricular myocytes using the whole-cell voltage-clamp technique. The shape of the I–V relation was unaffected by temperature (21–37°C) but there were large changes in I_Ca amplitude and time course. Steady-state responses indicated Q₁₀ 's of 2.96±0.14 (amplitude), 2.52±0.13 (time to peak), and 2.82±0.28 (T_1/2 inactivation) (mean ± SD, n=6). Quick changes in temperature (T_1/2<30 s) induced pronounced deviations from the steady-state Q₁₀ relations (early depression, compensatory overshoot). Thus, cardiac I_Ca differs from other currents in having a high amplitude-Q₁₀ and an oscillatory response to rapid temperature changes.     

Measurement of Krogh's diffusion constant of CO2 in respiring muscle at various CO2 levels: Evidence for facilitated diffusion

Summary Krogh's diffusion constant for CO₂, K_CO2, was determined in respiring muscle tissue at various levels of tissueP _CO2, between 10 and 160 torr, using a technique described previously (Kawashiro et al., 1975).With increasing mean tissueP _CO2, K_CO2 declined towards an apparently asymptotic value. The relationship between K_CO2 (10^–9 mmol·cm^–1·min^–1·torr^–1) andP _CO2 (torr) at 37° C could be approximated by the equation K_CO2=17.3 {1+1.72·exp(-0.027{P _CO2)}AtP _CO2=0 toor K_CO2 exceeded the asymptotic value, which was virtually attained atP _CO2=100 torr, by more than a factor of two. Thus CO₂ diffusion in muscle appears to be facilitated in the lowP _CO2 range.Specific CO₂ production rate of tissue, which was determined simultaneously, did not vary with CO₂ in theP _CO2 range studied.Effects of facilitated CO₂ transport on CO₂ exchange in muscle are assessed using simple models. In the presence of CO₂ facilitation muscleP _CO2 is reduced, particularly during exercise.     

Effect of secretin and inhibitors of HCO3 −/H+ transport on the membrane voltage of rat pancreatic duct cells

The aim of the present study was to study the effect of secretin on the electrophysiological response of pancreatic ducts. Furthermore, we investigated the effects of lipid-soluble buffers and inhibitors of HCO₃ ^–/H⁺ transport. Ducts obtained from fresh rat pancreas were perfused in vitro. Secretin depolarized the basolateral membrane voltage, V _bl, by up to 35 mV (n=37); a halfmaximal response was obtained at 3×10^–11 mol/l. In unstimulated ducts a decrease in the luminal Cl^– concentration (120 to 37 mmol/l) had a marginal effect on V _bl, but after maximal secretin stimulation it evoked a 14±2 mV depolarization (n=6), showing that a luminal Cl^– conductance G _Cl- was activated. The depolarizing effect of secretin on V _bl was often preceded by about a 6 mV hyperpolarization, most likely due to an increase in the basolateral G _K+. Perfusion of ducts with DIDS (4,4 — diisothiocyanatostilbene — 2,2 — disulphonic acid, 0.01 mmol/l) or addition of ethoxzolamide (0.1 mmol/l) to the bath medium diminished the effect of secretin. Acetate or pre-treatment of ducts with NH₄ ⁺/NH₃ (10 mmol/l in the bath) depolarized the resting V _bl of –65±2 mV by 16±4 mV (n=7) and 19±3 mV (n=10), respectively. The fractional resistance of the basolateral membrane (FR _bl) doubled, and the depolarizing responses to changes in bath K⁺ concentrations (5 to 20 mmol/l) decreased from 22±1 to 11±2 mV. The Na⁺/H⁺ antiporter blocker EIPA (5-[N-ethyl-N-isopropyl]-amiloride, 0.1 mmol/l) also depolarized V _bl by 10±1 mV, FR_bl increased and the response to K⁺ concentration changes decreased (n=7). Effects of EIPA and ethoxzolamide on V _bl were greater in ducts deprived of exogenous HCO₃ ^–/CO₂. Taken together, the present study shows that secretin increased the basolateral G _K+ and the luminal G _Cl-. The depolarizing effect of secretin was diminished following inhibition of HCO₃ ^– transport (DIDS), or HCO₃ ^–/H⁺ generation (ethoxzolamide). Manoeuvres that presumably led to lowered intracellular pH (NH₄ ⁺/NH₃ removal, acetate, EIPA) decreased the basolateral G _K+. The present data support our previously published model for pancreatic HCO₃ ^– secretion, and indicate that the basolateral membrane possesses a pH-sensitive G _K+.     

Na currents and action potentials in rat myelinated nerve fibres at 20 and 37° C

(1) Action potentials and membrane currents were recorded in single myelinated rat nerve fibres at 20 and 37° C. Three experiments were also performed in single cat nerve fibres. (2) K currents were blocked by internal CsCl and external TEA. The steady state and kinetic parameters of Na activation and inactivation were determined at both temperatures. (3) When the temperature was raised from 20 to 37° C, steady state Na activation,m (V), and inactivation,h (V), did not change significantly. (4) The time constant of Na activation, _m, was determined within the potential range of –40 to 125 mV at 20° C andV=40–60 mV at 37° C. The temperature coefficient, Q₁₀, of _m was 2.2. (5) The decay in the Na current was described by two exponentials at both temperatures. The amplitude of the slow phase was 1–10%. The time constant of the fast phase of Na inactivation, _h1, was determined at both temperatures within the potential range of –50 mV to 125 mV. The Q₁₀ of _h1 was 2.9 and did not depend on potential. (6) The Na equilibrium potential was 152 mV at 20° C and 144 mV at 37° C. The leakage conductance was 24 nS at 20° C and 43 nS at 37° C. These differences were interpreted as signs of fibre deterioration at higher temperature. (7) The results from the current and voltage clamp experiments performed in the cat nerve were essentially the same as those in the rat nerve fibres. (8) The action potentials computed on the basis of the voltage clamp results at 20° C were similar to the ones actually measured. This was also true for those action potentials predicted for 37° C on the basis of the 20° C data, theg _L andV _Na values measured at 37° C, and the Q₁₀ values of the time constants. (9) Steady state values and kinetic parameters of K permeability were adopted from the literature. As in the experiments the influence ofP _K on the shape of the predicted action potential was almost negligible at both temperatures.