Central chemoreceptor stimulus in the terrestrial,pulmonate snail,Helix aspersa

We studied the effect of hypercapnic and fixed acid central chemoreceptor stimulation on the pneumostone in the pulmonate snail, Helix aspersa. We found that focal stimulation of the central chemoreceptor area of the pulmonate snail brain with hypercapnic solutions more effectively increased the pneumostonal area than did fixed acid stimulation at the same extracellular pH. Disrupting intracellular pH regulation by inhibiting Cl⁻ transport, either pharmacologically (DIDS) or by ion substitution (Cl⁻-free perfusate), enhanced pneumostomal responses to CO₂. While maintaining a constant perfusate pH, addition of NH₄Cl to the perfusate resulted in pneumostomal closure; whereas removal of NH₄Cl from the bath resulted in pneumostomal opening. In conclusion, the ventilatory response to CO₂ in H. aspersa does not require Cl⁻ transport or conductance. Furthermore, changing pH_i alone is an adequate stimulus for the central chemoreceptors in the snail.     

Integration of bronchomotor and ventilatory responses to chemoreceptor stimulation in developing sheep

We analyzed the changes induced by central chemoreceptor stimulation on the lung resistances and phrenic neurogram of anesthetized newborn (3–6 days, n=9) and 9 week old lambs (n=3). Starting from hypocapneic apnea, 5% CO₂ inhalation evoked a reversible increase in total lung resistance in both newborn and 9 week old lambs (median=112%). The resistance increase preceded phrenic breathing and was greater for the peripheral (233%) than for the central airways (57%), independent of age. Increases in lung and airway resistance caused by CO₂ were reversed totally by atropine and only partially by apnea-producing doses of fentanyl. Our results demonstrate that parasympathetic outflow to the sheep airways is already driven by central chemoreceptor inputs during the newborn period. Even at this early age, bronchomotor responses to central chemoreceptor stimulation are more prominent in the peripheral than in the central airways and exhibit a lower threshold for activation and less sensitivity to opioid inhibition than phrenic responses.     

Acid-base balance and the control of respiration during anaxic and anoxic-hypercapnic gas breathing in turtles

We studied the ventilatory and blood acid-base response of turtles to 6 of breathing eithe 100% N₂(anoxic) or 95% N₂-5% CO₂ (anoxic-hypercapnic). In both groups, minute ventilation (V̇E) increased promptly with anoxia, with peak ventilation occurring between 1 and 3 h. V̇E then decreased but was still significantly above control at 6h. The increase in V̇E resulted from increases in both respiratory frequency (f) and tidal volume (VT) but after ventilation peaked, f declined to control while VT remained elevated. We observed no significant differences in V̇E between the two groups in spite of significantly lower arterial pH and higher arterial P_CO2 in the anoxic-hypercapnic turtles. During normoxic recovery, V̇E quickly increased to the peak anoxic values due primarily to a greatly increased f. In both groups, plasma [lactate⁻] increased during anoxia. Plasma cation concentrations also increased, partially compensating for the elevated blood lactate. We conclude that the anoxic hyperventilation did not depend on arterial pH and central chemoreceptor control but rather on peripheral hypoxic chemoreceptor control. We believe that the decline in V̇E during prolonged anoxic breathing results from a metabolic arrest response and/or a depression in central nervous function.     

Tachykinin antagonists in carotid body responses to hypoxia and subtance P in the rat

In the present study, we tested the hypothesis that substance P (SP) is an excitatory peptide to the rat carotid body and plays an important role in chemosensory excitation by hypoxia. Chemosensory discharge was recorded from the cut carotid sinus nerve in 19 anaesthetized, paralyzed and mechanically ventilated rats. Intracarotid admininstration of SP augmented the chemoreceptor activity in a dose-dependent manner. Maximal excitation was seen with 10 nmol SP. Carotid body stimulation by SP was independent of its effects on arterial blood pressure. The effect of SP antagonist, D-Pro²-D-Trp^7.9-SP (DPDT-SP) or Spantide, on chemoreceptor responses to SP and hypoxia was examined in 12 rats. Close carotid body administration of either at doses of 40 μg·kg⁻¹·min⁻¹ elicited an augmentation followed by a progressive depression of baseline carotid body activity. SP antagonists significantly reduced peptide-induced carotid body stimulation and also markedly attenuated the chemoreceptor response to hypoxia. Systemic administration of sodium bicarbonate stimulated the carotid bodies, presumably by releasing CO₂, and the bicarbonate-induced chemoreceptor stimulation was not affected by SP antagonists. From the results the conclude that in rats (a) SP stimulates the carotid bodies independently of its effects on arterial blood pressure, and (b) SP is associated with the chemosensory stimulation by hypoxia but not with other excitatory stimuli.     

Intracisternal diethylpyrocarbonate inhibits central chemosensitivity in conscious rabbits

As a direct chemical test of the alpha-imidazole hypothesis for the function of mammalian central chemoreceptors (CCR), diethylpyrocarbonate (DEPC) a relatively specific reactant with imidazole groups in vitro has been administered in vivo via intracisterna magna (ICM) infusion in conscious rabbits using each rabbit as its own control. DEPC, in a dose-dependent fashion, induced resting hypoventilation and inhibited (1) the ventilatory response to CO2 in peripherally chemodenervated animals, and (2) both the PaCO2 and minute ventilation responses to ICM infusion of an acidic mock cerebrospinal fluid (CSF). DEPC had no effect on the hypoxic ventilatory response and had small non-dose-dependent effects on body temperature. ICM administration of hydroxylamine (HDA), a substance that reverses the DEPC-imidazole binding in vitro, prevented DEPC induced inhibition of CCR function. These data support but do not prove the alpha-imidazole hypothesis for mammalian central chemoreceptor function and demonstrate a potentially useful chemical tool for the study of central chemoreception.     

Effects of central and peripheral chemoreceptor stimulation on ventilation in the marine toad, Bufo marinus

The contributions of central and peripheral chemoreceptors to respiratory control in lightly anesthetized Bufo marinus, were assessed by measuring the ventilatory responses to unidirectional ventilation (UDV) of the lungs at several concentrations of CO2 or O2, during intracranial perfusion (ICP) with hypercapnic acidic (5% CO2, pH 7.2) or hypocapnic alkaline (0% CO2, pH 8.3) mock CSF solutions. Peripheral chemoreceptor stimulation alone (hypoxia or hypercapnia during ICP with hypocapnic alkaline CSF) significantly increased breathing frequency and amplitude. ICP with hypercapnic acidic CSF further stimulated ventilation, primarily by significantly increasing the number of breaths/bout of breathing and decreasing the non-ventilatory time at all levels of peripheral ventilatory drive. When peripheral and central chemoreceptor stimulation was low toads were apneic. Stimulation of either central or peripheral chemoreceptors was sufficient to reinitiate breathing. Responses to ICP were greatest when perfusion was directed to the ventral medullary surface (VMS). These results suggest that the initiation of breathing and overall levels of breathing are functions of the combined afferent input from peripheral chemoreceptors and central CO2/pH sensitive chemoreceptors, located near the VMS. Stimulation of central chemoreceptors, however, produced longer duration bouts of rhythmic breathing than did peripheral chemoreceptor stimulation.     

Ocean acidification slows nitrogen fixation and growth in the dominant diazotroph Trichodesmium under low-iron conditions

Dissolution of anthropogenic CO₂ increases the partial pressure of CO₂ (pCO₂) and decreases the pH of seawater. The rate of Fe uptake by the dominant N₂-fixing cyanobacterium Trichodesmium declines as pH decreases in metal-buffered medium. The slower Fe-uptake rate at low pH results from changes in Fe chemistry and not from a physiological response of the organism. Contrary to previous observations in nutrient-replete media, increasing pCO₂/decreasing pH causes a decrease in the rates of N₂ fixation and growth in Trichodesmium under low-Fe conditions. This result was obtained even though the bioavailability of Fe was maintained at a constant level by increasing the total Fe concentration at low pH. Short-term experiments in which pCO₂ and pH were varied independently showed that the decrease in N₂ fixation is caused by decreasing pH rather than by increasing pCO₂ and corresponds to a lower efficiency of the nitrogenase enzyme. To compensate partially for the loss of N₂ fixation efficiency at low pH, Trichodesmium synthesizes additional nitrogenase. This increase comes partly at the cost of down-regulation of Fe-containing photosynthetic proteins. Our results show that although increasing pCO₂ often is beneficial to photosynthetic marine organisms, the concurrent decreasing pH can affect primary producers negatively. Such negative effects can occur both through chemical mechanisms, such as the bioavailability of key nutrients like Fe, and through biological mechanisms, as shown by the decrease in N₂ fixation in Fe-limited Trichodesmium.     

The effect of pH on 86Rubidium efflux from pancreatic islet cells

The influence of pH on the K⁺ permeability of pancreatic islet cells was investigated by measuring ⁸⁶Rb⁺ fluxes in isolated rat islets perifused or incubated in the absence of glucose. Acidification of the medium (to pH 6.5), by decreasing the concentration of HCO^?₃ or by increasing pCO₂ at constant HCO^?₃ reversibly reduced the rate of ⁸⁶Rb⁺ efflux from perifused islets. Alkalinization of the medium (to pH 7.8), by decreasing the pCO₂, reversibly increased ⁸⁶Rb⁺ efflux. Similar changes were recorded upon alteration of the pH in a bicarbonate-free, Hepesbuffered medium with or without calcium. Alteration of the CO₂ level at constant external pH — in order to modify internal pH — produced only a small and transient increase in efflux rate when CO₂ was lowered, and a decrease in efflux rate when CO₂ was raised. NH₄Cl reversibly augmented ⁸⁶Rb⁺ efflux in the presence and in the absence of HCO^?₃. At low pH (6.5), ⁸⁶Rb⁺ uptake by islet cells was reduced after 10 min (25%) and 30 min (11%), but not after 60 min, of incubation; it was not significantly affected by high pH (7.8). Calcium uptake and insulin release were reduced at low pH and increased at high pH.These results show that the K⁺ permeability of islet cells is affected by changes in extracellular but not in intracellular pH. They suggest that the endogenous production of protons that accompanies glucose stimulation of islet cells is not the mediator of the decrease in K⁺ permeability induced by the sugar.     

CO2 and naloxone modify sleep/wake state and activate breathing in the acute fetal lamb preparation

We studied locally anesthetized lamb fetuses (140–144 days' gestation) in utero on the day of surgical preparation (the acute preparation) to correlate sleep/wake (S/W) states with fetal breathing movements (FBM) activated by CO₂ with and without endorphin displacement by naloxone. We placed electrodes for definition of S/W states, a carotoid arterial catheter for injections and measurements of pressure, pHa, Pa_CO2 and Pa_CO2, and intratracheal and intraesophageal catheters for measurement of FBM and esophageal motility. We recorded the onset, pattern and cessation of breathing and estimated fetal respiratory responsitivity to CO₂ rebreathing by the ewe using our fetal CO₂ test (Moss, I.R. and Scarpelli, E.M., 1979, J. Appl. Physiol. 47: 527–531). Activation of breathing by CO₂ either accompanied or followed wakefulness (W)/ FBM and W were sustained throughout CO₂ stimulation. Cessation of breathing after the CO₂ test was temporally associated with the resumption of sleep. When the test was started in active sleep (AS) and W, breathing threshold to CO₂ was lower than when it was started in quiet sleep (QS). Naloxone treatment (1) resulted in activation of FBM in association with W, (2) lowered CO₂ threshold as compared to that of CO₂ entered in QS without naloxone, and (3) caused greater FBM responses to CO₂ than without naloxone. These results extend previous reports from our laboratory in that they demonstrate the importance of W to normal respiratory responsivity to CO₂ in the acute fetal preparation and the possible role of endorphins in respiratory control.     

Inhibitory sympathetic action on the carotid body responses to sustained hypoxia

The mammalian carotid bodies receive sympathetic innervation from the superior cervical ganglion. The purposes of the present study were: (10 to investigate whether sympathetic innervation influences the carotid body response to hypoxia, and, if so, (2) to determine the involvement fo adrenoceptors in these influence. Chemo-sensory activity was recorded from clearly identifiable action potentials form the carotid sinus nerve in 20 anaesthetized, paralyzed and artificially ventilated cats. Chemoreceptor responses to sustained isocapnic hypoxia (30 min, duration) were compared before and after carotid body sympathectomy (n = 8 cats). In response to low P_CO2, chemoreceptor discharge increased during the first 10 min, and plateaued for the rest of the hypoxic challenge. After sympathectomy, chemoreceptor response in the initial 10 min was the same; whereas, the magnitude of the response in remaining 20 min was significantly greater than controls (P < 0.01). Systemic administration of SKF-86466, an α₂-adrenoceptor antagonist augmented the hypoxic response by 805 n = 6 cats. Ini presence of α₂-antagoonist, sympathectomy had no further effect on the hypoxic response, but the magnitude of potentiation was less than with intact sympathetic innervation (34% vs 80%; P < 0.01; n = 6 cats. From these results,it is concluded that (1) sympathetic innervation exerts an inhibitory influence on chemoreceptor response to sustained hypopxia, and (2) this inhibitory influence is mediated at least in part by α₂-adrenoceptors. The inhibitory effects of sympathetic innervations could be of importance in the efferent regulation of the carotid body activity during sustained hypoxia.     

Model of maltose-binding protein/chemoreceptor complex supports intrasubunit signaling mechanism

The Tar protein of Escherichia coli is unique among known bacterial chemoreceptors in that it generates additive responses to two very disparate ligands, aspartate and maltose. Aspartate binds directly to the periplasmic (extracytoplasmic) domain of Tar. Maltose first binds to maltose-binding protein (MBP). MBP then assumes a closed conformation in which it can interact with the periplasmic domain of Tar. MBP residues critical for binding Tar were identified in a screen of mutations that cause specific defects in maltose chemotaxis. Mutations were introduced into a plasmid-borne malE gene that encodes a mutant form of MBP in which two engineered Cys residues spontaneously generate a disulfide bond in the oxidizing environment of the periplasmic space. This disulfide covalently crosslinks the NH₃-terminal and COOH-terminal domains of MBP and locks the protein into a closed conformation. Double-Cys MBP confers a dominant-negative phenotype for maltose taxis, and we reasoned that third mutations that relieve this negative dominance probably alter residues that are important for the initial interaction of MBP with Tar. The published three-dimensional structures of MBP and the periplasmic domain of E. coli Tar were docked in a computer simulation that juxtaposed the residues in MBP identified in this way with residues in Tar that have been implicated in maltose taxis. The resulting model of the MBP-Tar complex exhibits good complementarity between the surfaces of the two proteins and supports the idea that aspartate and MBP may each initiate an attractant signal through Tar by inducing similar conformational changes in the chemoreceptor.     

Buffering characteristics of eel blood at the extreme conditions in the swimbladder

CO₂ binding in whole blood and true plasma of the eel was estimated by measuring CO₂ content and pH in blood aliquots equilibrated with various P_CO2 values over a wide range expected to occur in the swimbladder. Bicarbonate concentration, [HCO₃⁻], was calculated using the CO₂ solubility coefficient, which was measured to average 50 μmol·L⁻¹·Torr⁻¹ (20°C). Buffer lines of non-bicarbonate buffers were obtained in plots of [HCPO₃⁻] against pH, and non-bicarbonate buffer values, β_NB, were obtained by curve. fitting.In the pH range 6.6–8.2, the buffer line for oxygenated whole blood was sigmoid, while that for deoxygenated blood increased its slope monotonously with increasing pH. The β_NB for oxygenated blood displayed a maximum of about 8.6 mmol·L⁻¹pH⁻¹ at pH = 7.4 and dropped down to below 1 mmol·L⁻¹·pH⁻¹ at higher and lower pH. Similar shapes of the buffer lines were obtaned in true plasma; the [HCO₃⁻] levels and β_NB values were, however, somewhat higher than in whole blood.These data are useful fo assess the back-diffusion of CO₂ and HCO₃⁻ in the rete mirabile of the fish swimbladder and to estimate the effects CO₂ back-diffusion exerts on the counter-current enhancement of O₂ in the rete.     

A physiologically stable rat model for in vivo studies

A physiologically stable rat model was developed to allow in vivo microcirculatory studies for up to 4 hr. Adult male Sprague-Dawley rats (200–250 g) underwent venous and arterial cannulation, tracheotomy and mechanical ventilation, and constant intravenous infusion of maintenance fluid and anesthesia. Heart rate, central venous pressure, arterial pressure, pH, pCO₂, pO₂, and rectal temperature were monitored and shown to be stable in the physiological range for 4 hr. This model is applicable to a wide variety of in vivo studies in circulatory, respiratory, and muscle physiology.     

Effects of M1-selective antimuscarinics on respiratory chemosensitivity in humans

We examined effects of selective M₁ antagonists on hypercapnic and hypoxic ventilatory responses in 17 healthy human volunteers. Subjects were intravenously treated with placebo, pirenzepine (10 mg) and biperiden lactate (4 mg) on three separate days in a randomized double-blind design. Ventilatory responses to hyperoxic progressive hypercapnia and isocapnic progressive hypoxia were studied after the drug administration. There were no statistically significant differences in the mean ΔV̇e/ΔPet_CO2 or ΔV̇e/ΔSa_O2 among the three treatments. However, the ΔV̇e/ΔPet_CO2 with placebo negatively correlated with the difference in ΔV̇e/ΔPet_CO2 between the biperiden and placebo studies (r = −0.65, P < 0.01), but not with that between the pirenzepine and placebo studies. On the other hand, the V̇e/ΔSa_O2 with placebo negatively correlated with the difference in V̇e/ΔSa_O2 between the pirenzepine and placebo studies (r = −0.79, P < 0.001), but not with that between the biperiden and placebo studies. These data suggest the possible involvement of M₁ cholinergic receptors in the central CO₂ and peripheral O₂ sensing mechanisms in humans, although the degree of its involvement is not consistent among subjects. These findings may explain the interindividual variation in the control of breathing in humans.     

Identification of the prooxidant site of human ceruloplasmin: A model for oxidative damage by copper bound to protein surfaces

Free transition metal ions oxidize lipids and lipoproteins in vitro; however, recent evidence suggests that free metal ion-independent mechanisms are more likely in vivo. We have shown previously that human ceruloplasmin (Cp), a serum protein containing seven Cu atoms, induces low density lipoprotein oxidation in vitro and that the activity depends on the presence of a single, chelatable Cu atom. We here use biochemical and molecular approaches to determine the site responsible for Cp prooxidant activity. Experiments with the His-specific reagent diethylpyrocarbonate (DEPC) showed that one or more His residues was specifically required. Quantitative [¹⁴C]DEPC binding studies indicated the importance of a single His residue because only one was exposed upon removal of the prooxidant Cu. Plasmin digestion of [¹⁴C]DEPC-treated Cp (and N-terminal sequence analysis of the fragments) showed that the critical His was in a 17-kDa region containing four His residues in the second major sequence homology domain of Cp. A full length human Cp cDNA was modified by site-directed mutagenesis to give His-to-Ala substitutions at each of the four positions and was transfected into COS-7 cells, and low density lipoprotein oxidation was measured. The prooxidant site was localized to a region containing His⁴²⁶ because Cp_H426A almost completely lacked prooxidant activity whereas the other mutants expressed normal activity. These observations support the hypothesis that Cu bound at specific sites on protein surfaces can cause oxidative damage to macromolecules in their environment. Cp may serve as a model protein for understanding mechanisms of oxidant damage by copper-containing (or -binding) proteins such as Cu, Zn superoxide dismutase, and amyloid precursor protein.     

A study of temporal relation between intracellular pH and contractile performance in toad ventricular strips during hypercapnic acidosis

Experiments were performed on toad (Bufo marinus) ventricular strips to determine the temporal relation between the decrease in intracellular pH (pH_i) and the changes in mechanical performance accompanying increases in P_CO2. Changes in pH_i were measured with a dual wavelength spectrophotometer using the pH sensitive dye neutral red. Regardless of whether the superfusate pH (pH₀) or [HCO₃^?] was held constant, changes in P_CO2 were accompanied by a monotonic, biphasic change in pH_i. A plot of 1n ΔpH_i v. t consistently yielded a curvilinear line which was well fit by two straight lines. The developed tension also exhibited a biphasic response to ΔP_CO2: an initial decrease followed by a rebound which returned τ to control values (98.4 ± 1.6%) after 30 min. The onset of the second, slow phase of acidification correlated well (r = 0.83) with the onset of the mechanical rebound. The time of this onset was affected by [HCO₃^?]. Further experiments showed that with P_CO2 held constant, a decrease in [HCO₃^?] was accompanied by a slow decrease in pH_i. The data from these experiments suggest that: (1) changes in P_CO2 affect the pH of at least two intracellular compartments and these effects are temporally dissociated; (2) the response of the faster compartment correlates with the initial decrease of τ; the response of the slower with the rebound of τ; (3) when P_CO2 is held constant, decreases in pH₀ are accompanied by a slow decrease in pH_i suggesting a possible H⁺ or [HCO₃^?] leak.     

Effect of acute hypoxia on metabolism and ventilation in awake piglets

We studied the effect of acute sustained hypoxia on ventilation (V̇e) and oxygen consumption (V̇_O2) over one hour during quiet wakefulness in young (6 days) and older (6 weeks) piglets in thermoneutral conditions during baseline, moderate hypoxia(Pa_O2 ≈ 45 mmHg). During severe hypoxia, ventilation and pH increased while Pa_CO2 decreased in both age groups. Blood gas changes(↓PA_CO2, ↑pH), but not ventilatory changes, were greater in the older piglets(P < 0.05).V̇_O2 decreased similarly (− 30%) whileV̇e/V̇_O2 rose over 160% in both age groups. During moderate hypoxia, changes in blood gas, V̇e, andV̇_O2 were in similar direction, but smaller in magnitude. We conclude that: (1) changes in blood gases andV̇_O2 are amplified by maturation and severity of hypoxia and (2) blood gas changes are greater in oldervs young piglets despite similar ventilatory responses suggesting maturational differences in CO₂ production or dead space ventilation.     

Acute respiratory failure and obesity with normal ventilatory response to carbon dioxide and absent hypoxic ventilatory drive

We measured hypoxic and hypercapnic ventilatory drive in a 64 year old woman with acute respiratory failure, congestive heart failure and obesity when she was in remission. She had a ventilatory response to carbon dioxide (CO₂) comparable to that in six obese women without hypoventilation but no ventilatory response to hypoxia or to vital capacity breaths of 15 per cent CO₂ in N₂- Following weight loss, her ventilatory response to CO₂ increased but hypoxic ventilatory drive remained absent. These findings indicate that attenuation of hypoxic ventilatory drive caused by loss of peripheral chemoreceptor function can be a predisposing factor in the development of acute respiratory failure associated with obesity.     

Omeprazole induces altered bile acid metabolism

Background—It has been reported that the acidityof gastric contents could be an important factor in regulating jejunal flora.
Aims—To investigate the effects of omeprazoleinduced changes in gastric pH on jejunal flora and bile acid metabolism.
Methods—Twenty one patients with gastric ulcer and19 healthy volunteers were studied. Deconjugation of bile acids wasdetected using a bile acid breath test. Jejunal fluid was aspiratedusing a double lumen tube with a rubber cover on the tip anddeconjugation was examined using thin layer chromatography. Fatmalabsorption was detected by a triolein breath test.
Results—In the bile acid breath test, expiredbreath samples from all patients and healthy volunteers showedsignificantly greater ¹⁴CO₂ specific activityafter omeprazole treatment (20 mg/day) than before treatment. Bacterialovergrowth was found in the jejunal fluid and gastric juice of bothulcer patients and healthy volunteers after omeprazole treatment. Thefollowing species were identified: Escherichia coli,Candida albicans, enterococcus, Lactobacillus bifidus, Bacteroides vulgatus, Buniformis, Eubacterium lentum, Euparvum, and Corynebacterium granulosum. All ofthese species, except E coli and C albicans,deconjugate bile acids. There was a significant correlation between¹⁴CO₂ activity and gastric pH, both before andafter omeprazole treatment in both groups. The triolein breath testrevealed impaired fat absorption in both groups after omeprazole treatment.
Conclusions—Both patients with gastric ulcer andhealthy volunteers exhibited increased deconjugation of bile acidscaused by bacterial overgrowth in the jejunum and fat malabsorptionafter omeprazole treatment. The bacterial overgrowth consisted of both anaerobes and aerobes with deconjugation ability and was probably associated with an omeprazole induced shift to neutral pH in the gastric juice.

Keywords:omeprazole; bacterial overgrowth; deconjugation; bile acid breath test; gastric pH; gastric ulcer

     

The importance of hydrology in routing terrestrial carbon to the atmosphere via global streams and rivers

The magnitude of stream and river carbon dioxide (CO₂) emission is affected by seasonal changes in watershed biogeochemistry and hydrology. Global estimates of this flux are, however, uncertain, relying on calculated values for CO₂ and lacking spatial accuracy or seasonal variations critical for understanding macroecosystem controls of the flux. Here, we compiled 5,910 direct measurements of fluvial CO₂ partial pressure and modeled them against watershed properties to resolve reach-scale monthly variations of the flux. The direct measurements were then combined with seasonally resolved gas transfer velocity and river surface area estimates from a recent global hydrography dataset to constrain the flux at the monthly scale. Globally, fluvial CO₂ emission varies between 112 and 209 Tg of carbon per month. The monthly flux varies much more in Arctic and northern temperate rivers than in tropical and southern temperate rivers (coefficient of variation: 46 to 95 vs. 6 to 12%). Annual fluvial CO₂ emission to terrestrial gross primary production (GPP) ratio is highly variable across regions, ranging from negligible (<0.2%) to 18%. Nonlinear regressions suggest a saturating increase in GPP and a nonsaturating, steeper increase in fluvial CO₂ emission with discharge across regions, which leads to higher percentages of GPP being shunted into rivers for evasion in wetter regions. This highlights the importance of hydrology, in particular water throughput, in routing terrestrial carbon to the atmosphere via the global drainage networks. Our results suggest the need to account for the differential hydrological responses of terrestrial–atmospheric vs. fluvial–atmospheric carbon exchanges in plumbing the terrestrial carbon budget.

The Earth’s water, carbon, and energy fluxes follow seasonal variations in the Earth’s solar radiation and climate variability (1, 2). As an integral part of terrestrial landscapes, streams and rivers receive significant water and carbon inputs from terrestrial and wetland ecosystems, which are further processed along the river to ocean continuum (3). As the largest carbon flux mediated by fluvial systems, carbon dioxide (CO₂) emission from stream and river surfaces (4–7) is double the lateral carbon transport to oceans (8), yet its spatial and temporal variations are not fully resolved. Stream and river CO₂ evasion changes considerably across space and time due to biogeochemical responses to climatic factors (3), the physics governing the transfer of gas across the water–air interface (9), and seasonal variations in the spatial extent of drainage networks (10, 11). However, seasonal variability of the flux has not been determined at the global scale, limiting our ability to understand controls at the macrosystem level.The rate at which streams and rivers exchange CO₂ with the atmosphere is determined by three factors: dissolved CO₂ concentration (often expressed as an equivalent atmospheric partial pressure [pCO₂]), water surface gas transfer velocity (k), and water surface area. To estimate flux at the monthly scale, all three factors need to be resolved at the same or finer temporal scale(s). To date, existing spatially explicit estimates of riverine CO₂ emission at the global scale (4, 12) relied exclusively on pCO₂ calculated from carbonate equilibria and historical archives of pH and alkalinity measurements. While these data have reasonable spatial coverage, the carbonate equilibria method is subject to inflated pCO₂ estimates due to biased pH measurements (13) and alkalinity contribution from organic acids (14), particularly in low–ionic strength waters. These errors, although reducible within individual datasets (15), are difficult to correct for when scaling globally. This problem has significantly undermined calculations and understanding of the flux at the global scale. More importantly, although global estimates of the stream and river surface area and gas transfer velocity at mean annual discharge have been achieved (4, 16), their seasonal extent, a major driver of within-year variability of riverine CO₂ flux, has not. This is largely because a temporally resolved reach-scale representation of global river hydrology has not been available until recently (17), and new understandings of aquatic surface area extent and water–air gas transfer rates are necessary to incorporate temporal variability into the riverine CO₂ flux estimate.We compiled a dataset of present-day direct pCO₂ measurements in global streams and rivers from the literature. The dataset has 5,910 individual measurements of different months that cover all major freshwater ecoregions of the world (18), despite a small percentage (∼0.5%) of measurements from southern temperate rivers (SI Appendix, Fig. S1). The dataset further has pCO₂ measurements in all months from each freshwater ecoregion (open water months for the polar freshwater ecoregion) except oceanic islands and large river deltas that make up only 0.4% of the global land area (SI Appendix, Fig. S1). These observations allowed for robust validation of the study’s results. Riverine pCO₂ was statistically modeled against a set of watershed properties (SI Appendix, Table S1) in order to understand biogeochemical and geophysical controls on pCO₂. Predictions of pCO₂, k, and surface area were based on a new representation of the global river networks (the Global Reach-Level A Priori Discharge Estimates for Surface Water and Ocean Topography [GRADES] river networks) (17), which contains daily discharge estimates at ∼3 million individual river reaches over a 35-y period. Monthly CO₂ flux estimates were achieved by coupling monthly pCO₂ estimates driven by monthly watershed properties to monthly k and surface area estimates driven by the GRADES discharge. Spatial and temporal variability of the flux was finally investigated to demonstrate a strong modulation of the terrestrial (and wetland) carbon routing to the atmosphere via streams and rivers by hydrology.