Mikko Nikinmaa
University of Turku, Department of Biology, Faculty Member
- I am an environmental scientis, focusing especially on the effects on fish. I and my coworkers have studied especiall... moreI am an environmental scientis, focusing especially on the effects on fish. I and my coworkers have studied especially the acclimation and adaptation to hypoxia and temperature changes and how environmental pollution disturbs the adaptive responses.edit
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Research Interests: Biology, Cell Cycle, Survival Analysis, Medicine, Gene expression, and 15 moreBiological Sciences, real time PCR, Microarray, Animals, Cell Death, Salmon, Histones, Microarray Analysis, Environmental Stress, Cdna Microarray, Cell Proliferation, Gene expression profiling, Differential expression, BMC, and Medical and Health Sciences
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Ectotherms can respond to climate change via evolutionary adaptation, usually resulting in an increase of their upper thermal tolerance. But whether such adaptation influences the phenotypic plasticity of thermal tolerance when... more
Ectotherms can respond to climate change via evolutionary adaptation, usually resulting in an increase of their upper thermal tolerance. But whether such adaptation influences the phenotypic plasticity of thermal tolerance when encountering further environmental stressors is not clear yet. This is crucial to understand because organisms experience multiple stressors, besides warming climate, in their natural environment and pollution is one of those. Here, we studied the phenotypic plasticity of thermal tolerance in three-spined stickleback populations inhabiting spatially replicated thermally polluted and pristine areas before and after exposing them to a sublethal concentration of copper for one week. We found that the upper thermal tolerance and its phenotypic plasticity after copper exposure did not depend on the thermal history of fish, suggesting that five decades of thermal pollution did not result in evolutionary adaptation to thermal tolerance. The upper thermal tolerance of fish was, on the other hand, increased by ∼ 1.5 °C after 1-week copper exposure in a sex-specific manner, with males having higher plasticity. To our knowledge this is the first study that shows an improvement of the upper thermal tolerance as a result of metal exposure. The results suggest that three-spined sticklebacks are having high plasticity and they are capable of surviving in a multiple-stressor scenario in the wild and that male sticklebacks seem more resilient to fluctuating environmental conditions than female.
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AimWe studied whether available oxygen without induced mechanical stretch regulates the release of the biologically active B‐type natriuretic peptide (BNP) from Langendorff heart.MethodsRat hearts were isolated and perfused with a... more
AimWe studied whether available oxygen without induced mechanical stretch regulates the release of the biologically active B‐type natriuretic peptide (BNP) from Langendorff heart.MethodsRat hearts were isolated and perfused with a physiological Krebs–Henseleit solution at a constant hydrostatic pressure in Langendorff set‐up. The basal O2 level of perfusate (24.4 ± 0.04 mg L−1) was gradually lowered to 3.0 ± 0.01 mg L−1 over 20 min using N2 gas (n = 7). BNP and O2 level were measured from coronary flow. During control perfusions (n = 5), the O2 concentration was kept at 26.6 ± 0.3 mg L−1.ResultsA low oxygen concentration in the perfusate was associated with a significant increase in BNP release (F = 40.4, P < 0.001). Heart rate decreased when the oxygen concentration in the perfusate reached 9.1 ± 0.02 mg L−1 and continued to fall in lower oxygen concentrations (F = 14.8, P < 0.001). There was also a significant but inverse correlation between BNP and oxygen in the coronary fl...
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Much adaptive evolutionary change is underlain by mutational variation in regions of the genome that regulate gene expression rather than in the coding regions of the genes themselves. An understanding of the role of gene expression... more
Much adaptive evolutionary change is underlain by mutational variation in regions of the genome that regulate gene expression rather than in the coding regions of the genes themselves. An understanding of the role of gene expression variation in facilitating local adaptation will be aided by an understanding of underlying regulatory networks. Here, we characterize the genetic architecture of gene expression variation in the threespine stickleback (Gasterosteus aculeatus), an important model in the study of adaptive evolution. We collected transcriptomic and genomic data from 60 half-sib families using an expression microarray and genotyping-by-sequencing, and located QTL underlying the variation in gene expression (eQTL) in liver tissue using an interval mapping approach. We identified eQTL for several thousand expression traits. Expression was influenced by polymorphism in both cis and trans regulatory regions. Trans eQTL clustered into hotspots. We did not identify master transcri...
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The chapter first discusses the history of aquatic contamination, highlighting major cases where aquatic contamination has become an issue and cases where efficient solutions to environmental problems have been reached. Thereafter, the... more
The chapter first discusses the history of aquatic contamination, highlighting major cases where aquatic contamination has become an issue and cases where efficient solutions to environmental problems have been reached. Thereafter, the hierarchy of biological functions that can be disturbed by toxicants is briefly introduced. Notably, even when the ultimate goal of toxicological research is to find out how contamination affects an ecosystem, one must remember that the toxicants affect molecular functions of the most sensitive species. Toxicological testing and its uses are then introduced. The principal available aquatic toxicology testing methods, as given by the International Organization for Standardization (ISO) and the Organisation for Economic Co-operation and Development (OECD), are tabulated and the procedure for validating toxicity tests internationally is given. An overview of important issues for aquatic toxicological research in the future is also given.
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The nature of the swelling-activated K+ and Cl- transport pathways of lamprey (Lampetra fluviatilis) erythrocytes was studied. In isosmotic medium, unidirectional K+ and Cl- effluxes appear to be largely mediated by conductive pathways.... more
The nature of the swelling-activated K+ and Cl- transport pathways of lamprey (Lampetra fluviatilis) erythrocytes was studied. In isosmotic medium, unidirectional K+ and Cl- effluxes appear to be largely mediated by conductive pathways. Unidirectional Cl- efflux increased as a function of a decrease in medium osmolarity. The swelling-activated Cl- transport was inhibited by R(+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inde n-5- yl)oxy]acetic acid (DIOA), furosemide, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In contrast, moderate cell swelling did not increase unidirectional ouabain-insensitive K+ efflux. However, inhibition of transport by Ba2+ was markedly reduced. This suggests that the Ba(2+)-sensitive pathway that mediated most of the K+ efflux in isosmotic conditions was inhibited by cell swelling and a Ba(2+)-insensitive pathway was activated. DIOA had no effect on K+ efflux in isosmotic or hyposmotic medium. These data and the fi...
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Vertebrate red Blood cells : , Vertebrate red Blood cells : , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
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We studied the effects of prelytic copper concentrations on cell volume, intracellular pH, and ion transport in lamprey erythrocytes. Ion fluxes and pH were measured by radioactive tracer technique, patch clamp, and flame photometry.... more
We studied the effects of prelytic copper concentrations on cell volume, intracellular pH, and ion transport in lamprey erythrocytes. Ion fluxes and pH were measured by radioactive tracer technique, patch clamp, and flame photometry. Prelytic CuSO(4) concentration of 100 microM caused anion-dependent intracellular acidification and increase in Cl(-) influx after 2 min lag-phase. In the presence of ascorbate copper effect was amplified and lag-phase was skipped. Pretreatment of the cells with N-phenyl maleimide abolished copper-induced changes completely. Copper treatment caused an increase in Na(+) fluxes in both directions and a net Na(+) uptake. Copper-induced Na(+) transport was partially amiloride(MIA)-sensitive representing Na(+)/H(+) exchange. The nature of the amiloride-insensitive fraction of copper-activated Na(+) influx remains unknown. Cell swelling after 15 min of copper exposure induced regulatory volume decrease response involving KCl extrusion via K(+) and Cl(-) volume-sensitive channels. We suggest that the effects of copper on ion transport fit the following sequence of events: (i) cupric ions are reduced to cuprous state on the membrane surface, (ii) electroneutral pairs CuCl and CuOH mediate chloride/hydroxyl exchange, as shown before for trialkyltin, dissipating transmembrane pH gradient, and (iii) changes in intracellular pH result in the activation of the Na(+)/H(+) exchange and consecutive volume changes cause the RVD response.
Research Interests: Chemistry, Inorganic Chemistry, Medicine, Copper, Animals, and 15 morePotassium, Sodium, Ion Transport, Erythrocyte Membrane, Cations, Hydrogen-Ion Concentration, Regulatory volume decrease, Cell Volume, Patch Clamp, Chlorides, Volume change, Amiloride, reducing agents, Pharmacology and pharmaceutical sciences, and Ion transporter
Research Interests: Physiology, Zoology, Biology, Oxidative Stress, Medicine, and 15 moreFinland, South Africa, Animals, Oxidoreductases, Animal migration, Catalase, Glutathione Peroxidase, Medical Physiology, Superoxide Dismutase, Barn, Biotransformation, Seasons, Glutathione Transferase, Glutathione Reductase, and Swallows
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Migration is an energy-demanding life-history period and also a significant population-limiting factor of long-distance migratory birds. It is important to understand how corticosterone, the main energy regulating hormone in birds, is... more
Migration is an energy-demanding life-history period and also a significant population-limiting factor of long-distance migratory birds. It is important to understand how corticosterone, the main energy regulating hormone in birds, is associated with behavioural and physiological changes during migration. According to the migration modulation hypothesis (MMH), individual birds may express elevated levels of baseline corticosterone to facilitate fuelling, but down-regulate the adrenocortical response in order to protect skeletal muscles from the catabolic effects of the hormone. We measured the baseline and stress-induced levels of corticosterone in barn swallows (Hirundo rustica L.) during early stages of autumn migration. Here, we show that, while barn swallows clearly responded to the capture and handling stress by increasing the corticosterone level, the strength of this acute response was related to their energetic condition: birds with high body mass responded more rapidly and had lower peak values of corticosterone than lighter birds. Further, the baseline levels of corticosterone correlated negatively with the magnitude of the adrenocortical response. Barn swallows did not show elevated baseline levels of corticosterone in the course of autumn, which suggests that, instead of fuelling, the birds were actively migrating. Our results indicate that MMH also applies to aerial feeders, whose foraging habits differ from model birds of previous studies.
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We studied pH regulation in freshly isolated rainbow trout hepatocytes using microspectrofluorometry with the fluorescent dye BCECF. In accordance with earlier data on rainbow trout hepatocytes, ion substitution (N-methyl D-glucamine for... more
We studied pH regulation in freshly isolated rainbow trout hepatocytes using microspectrofluorometry with the fluorescent dye BCECF. In accordance with earlier data on rainbow trout hepatocytes, ion substitution (N-methyl D-glucamine for sodium and gluconate for chloride) and transport inhibitor [10 microM M methyl isobutyl amiloride (MIA) to inhibit sodium/proton exchange and 100 microM DIDS to inhibit bicarbonate transport] studies in either Hepes-buffered or bicarbonate/carbon dioxide-buffered media (extracellular pH 7.6) indicated a role for sodium/proton exchange, sodium-dependent bicarbonate transport, and sodium-independent anion exchange in the regulation of hepatocyte pH. In Hepes-buffered medium, the activity of the sodium/proton exchanger (i.e. proton extrusion inhibited by MIA) was greater at 1% than at 21% oxygen. The oxygen dependency of the sodium/proton exchange is not caused by hydroxyl radicals, which appear to mediate the oxygen sensitivity of potassium-chloride cotransport in erythrocytes.
Research Interests: Physiology, Chemistry, Carbon Dioxide, Fluorescent Dyes and Reagents, Medicine, and 15 moreAnimals, Membrane transport, Oxygen, Sodium, Hepatocytes, Rainbow trout, Bicarbonate, Oncorhynchus Mykiss, Protons, Potassium Chloride, Biochemistry and cell biology, Amiloride, fluorescent dyes, Hydroxyl Radical, and Bicarbonates
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Levels of oxygen can vary dramatically in aquatic environments. Aquatic organisms, including fishes, have adapted accordingly to survive. As there are both phylogenetically closely related fish species with differing oxygen requirements... more
Levels of oxygen can vary dramatically in aquatic environments. Aquatic organisms, including fishes, have adapted accordingly to survive. As there are both phylogenetically closely related fish species with differing oxygen requirements and distantly related species with similar oxygen requirements, fishes are good candidates for examining oxygen-related functions in vertebrates. We set out to investigate if sequence variation in the hypoxia-inducible factor-1 alpha (HIF-1alpha) gene is associated with variations in oxygen requirements. Since the teleost HIF-1alpha sequences available in databases represent a very limited dataset both phylogenetically and with regard to oxygen requirements, we have sequenced the protein coding sequence for HIF-1alpha from an additional 9 fish species. Our results indicate that the deduced HIF-1alpha proteins of teleost fishes are somewhat shorter than those of tetrapods. Additionally, the results suggest that tetrapod sequences more closely resemble the ancestral form of the protein than do teleost sequences. No clear signatures which could be associated with the oxygen requirements of the species were found. This study suggests that if species-specific differences in HIF-1alpha function with regards to oxygen dependence have evolved, they do not occur in the protein coding sequence but at other levels of the HIF-1alpha pathway.
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We have studied the mechanism of copper uptake by the cells, its oxidative action and effects on ion transport systems using rainbow trout erythrocytes. Cupric ions enter trout erythrocytes as negatively charged complexes with chloride... more
We have studied the mechanism of copper uptake by the cells, its oxidative action and effects on ion transport systems using rainbow trout erythrocytes. Cupric ions enter trout erythrocytes as negatively charged complexes with chloride and hydroxyl anions via the band 3-mediated Cl-/HCO3- exchanger. Replacement of Cl- by gluconate, and complexation of cupric ions with histidine abolish rapid Cu2+ uptake. Within the cell cupric ions interact with haemoglobin, causing methaemoglobin formation by direct electron transfer from heme Fe2+ to Cu2+, and consecutive proton release. Ascorbate-mediated reduction of cupric ions to cuprous decreases copper-induced metHb formation and proton release. Moreover, cuprous ions stimulate Na+H+ exchange and residual Na+ transport causing net Na+ accumulation in the cells. The effect requires copper binding to an externally facing thiol group. Copper-induced Na+ accumulation is accompanied by K+ loss occurring mainly via K+-Cl- cotransporter. Taurine efflux is also stimulated by copper exposure. However, net loss of osmolytes is not as pronounced as Na+ uptake and modest swelling of the cells occurs after 5 min of copper exposure. Taken together the results indicate that copper toxicity, including copper transport into the cells and its interactions with ion transport processes, depend on the valency and complex formation of copper ions.
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We studied the effects of dehydroabietic acid (DHAA), a major toxic resin acid in wood industry effluents, on cellular energetics in rainbow trout (Oncorhynchus mykiss) hepatocytes. In addition, the role of DHAA-induced change in... more
We studied the effects of dehydroabietic acid (DHAA), a major toxic resin acid in wood industry effluents, on cellular energetics in rainbow trout (Oncorhynchus mykiss) hepatocytes. In addition, the role of DHAA-induced change in intracellular Ca(2+) in the energetic responses of the cells was evaluated. At sublytic concentrations, DHAA caused a reduction in cellular ATP content and a concomitant enhancement of glycolytic activity of the cells in a dose-dependent manner. No further decrease of cellular ATP content occurred after 60 min of DHAA-treatment indicating establishment of new energetic steady state in cells. DHAA also caused a rapid dose-dependent increase in oxygen consumption and in cellular heat production of the hepatocytes. The effect of DHAA on ATP content and glycolytic activity was independent from Ca(2+), whereas, changes in oxygen consumption and heat production were Ca(2+) -dependent. These results show that DHAA induces energetic imbalance in rainbow trout hepatocytes, which is apparently not due to direct interference of DHAA with ATP production nor does it seem to be caused by an indirect effect of elevated intracellular Ca(2+) concentration on mitochondrial energetics. Therefore, the ATP depletion is likely due to increased cellular ATP consumption caused by amphiphilic action of DHAA on the cell membrane.
Research Interests: Biochemistry, Biophysics, Chemistry, Metabolism, Aquatic Toxicology, and 15 moreCalcium, Medicine, Biological Sciences, Environmental Sciences, FISH, Animals, Glycolysis, CHEMICAL SCIENCES, Diterpenes, Hepatocytes, Calorimetry, Membrane Fluidity, Adenosine Triphosphate, Intracellular, and Cell Membrane
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Evolutionary and acclimatory responses require functional variability, but in contrast with mRNA and protein abundance data, most physiological measurements cannot be obtained in a high-throughput manner. Consequently, one must either... more
Evolutionary and acclimatory responses require functional variability, but in contrast with mRNA and protein abundance data, most physiological measurements cannot be obtained in a high-throughput manner. Consequently, one must either rely on high-throughput transcriptomic or proteomic data with only predicted functional information, or accept the limitation that most physiological measurements can give fewer data than those provided by transcriptomics or proteomics. We evaluated how transcriptional and redox enzyme activity data agreed with regard to population differentiation (i.e. a system in steady state in which any time lag between transcription, translation and post-translational effects would be irrelevant) and in response to an acute 6°C increase in temperature (i.e. a disequilibrium state wherein translation could not have caught up with transcription) in the three-spined stickleback ( Gasterosteus aculeatus ). Transcriptional and enzyme activity data corresponded well wit...
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Neural systems exposed to diminished oxygen availability have a compromised metabolism that leads to pathophysiological changes or neuronal death, depending on the severity and duration of oxygen deprivation. A distributed network of... more
Neural systems exposed to diminished oxygen availability have a compromised metabolism that leads to pathophysiological changes or neuronal death, depending on the severity and duration of oxygen deprivation. A distributed network of oxygen sensors responds to protect cells by slowing or ameliorating pathophysiological changes and forestalling neuronal death via short-term and/or long-term changes involving gene expression and the modification of sensors and effectors. In mammalian systems such protective changes are not sufficient to prevent damage under extreme conditions, unlike some hypoxiaand anoxia-tolerant vertebrates which demonstrate an oxygen dependent and reversible reprogramming to protect vital organs such as the brain and heart. This review examines (1) the nature of the signal for oxygen sensors; (2) the molecules used to sense oxygen; (3) how the primary signal is generated, converted and used in an oxygen-dependent manner; (4) how effector systems function in differ...
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Neural systems exposed to diminished oxygen availability have a compromised metabolism that leads to pathophysiological changes or neuronal death, depending on the severity and duration of oxygen deprivation. A distributed network of... more
Neural systems exposed to diminished oxygen availability have a compromised metabolism that leads to pathophysiological changes or neuronal death, depending on the severity and duration of oxygen deprivation. A distributed network of oxygen sensors responds to protect cells by slowing or ameliorating pathophysiological changes and forestalling neuronal death via short-term and/or long-term changes involving gene expression and the modification of sensors and effectors. In mammalian systems such protective changes are not sufficient to prevent damage under extreme conditions, unlike some hypoxiaand anoxia-tolerant vertebrates which demonstrate an oxygen dependent and reversible reprogramming to protect vital organs such as the brain and heart. This review examines (1) the nature of the signal for oxygen sensors; (2) the molecules used to sense oxygen; (3) how the primary signal is generated, converted and used in an oxygen-dependent manner; (4) how effector systems function in differ...
In this study, we examined whether the adrenergic volume response of teleost erythrocytes is related to cell maturity. Rainbow trout (Oncorhynchus mykiss) were made anaemic by reducing their haematocrit to approximately 50 % of the... more
In this study, we examined whether the adrenergic volume response of teleost erythrocytes is related to cell maturity. Rainbow trout (Oncorhynchus mykiss) were made anaemic by reducing their haematocrit to approximately 50 % of the original value. After 3–4 weeks, small, young erythrocytes were seen in the circulation. By measuring the volume distribution of blood samples from anaemic fish before and after noradrenaline stimulation (10 min, 10(−5)mol l(−1) final concentration), we were able to show that the volume response of young, immature erythrocytes to catecholamine stimulation was greater than that of mature erythrocytes. In addition, the membrane fluidity, measured using the steady-state fluorescence polarisation method, was greater in anaemic fish after 24 days of recovery from bleeding than in control fish. Since blood from anaemic fish contained a large fraction of immature erythrocytes, this result indicates that the fluidity of the membrane of immature erythrocytes is gr...
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In the present study, we have examined the adrenergic responses of Arctic charr (Salvelinus alpinus) erythrocytes acclimated to different temperatures (2, 8 and 14 degrees C) during different seasons. We measured the changes in cellular... more
In the present study, we have examined the adrenergic responses of Arctic charr (Salvelinus alpinus) erythrocytes acclimated to different temperatures (2, 8 and 14 degrees C) during different seasons. We measured the changes in cellular water and ion contents after noradrenaline stimulation using different noradrenaline concentrations and external pH values. Furthermore, the effects of acute temperature changes on the magnitude of the adrenergic response were studied. The adrenergic response of Arctic charr erythrocytes showed pronounced seasonal variation. The [Na(+)]/[Cl(−)] accumulation ratio after adrenergic stimulation was greatest in May, indicating an enhanced activity of the Na(+)/H(+) exchanger. The noradrenaline-induced change in [Na(+)](i) was greatest in spring. In addition to a seasonal effect, the exchanger seemed to be most active in erythrocytes from charr acclimated to low temperature (2 degrees C) early in May: the EC(50) value was lower and the calculated maximal ...
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Haemoglobin function within lamprey erythrocytes offers a unique solution to gas transport among vertebrates. Lamprey haemoglobin within intact erythrocytes is in oligomer/monomer equilibrium and has an oxygen affinity similar to that of... more
Haemoglobin function within lamprey erythrocytes offers a unique solution to gas transport among vertebrates. Lamprey haemoglobin within intact erythrocytes is in oligomer/monomer equilibrium and has an oxygen affinity similar to that of haemoglobin in other active fishes. The cooperativity of oxygen binding, which is reduced at low pH values, the effect of protons and the effect of the concentration of haemoglobin on its oxygen affinity are all due to dissociation/association reactions of the haemoglobin molecules. The permeability of the lamprey red cell membrane to acid and base equivalents is very low, and plasma bicarbonate cannot therefore be dehydrated to carbon dioxide to any significant extent during the residence time of blood in the gills. This potential limitation on carbon dioxide excretion is overcome, however, by the high intraerythrocytic pH and the marked oxygenation-linked pH changes in the erythrocyte, which are due to the large Haldane effect of the haemoglobin. ...
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Carp (Cyprinus carpio) red cells do not show beta-adrenergic responses when incubated with 10(−5) mol l-1 adrenaline at atmospheric oxygen tension and a pH value close to the in vivo resting pH (approx. 8.1). However, when either the pH... more
Carp (Cyprinus carpio) red cells do not show beta-adrenergic responses when incubated with 10(−5) mol l-1 adrenaline at atmospheric oxygen tension and a pH value close to the in vivo resting pH (approx. 8.1). However, when either the pH or the oxygen tension of the incubation medium is decreased, the adrenergic responses appear, showing that oxygen or an oxygen-linked phenomenon has a direct influence on the response. Once present, the adrenergic red cell response is similar to that of trout: cellular water content, sodium content and intracellular pH all increase. Quantitatively the effect appears to be much smaller in carp than in trout. Adrenaline induces an increase in red cell oxygen content when the oxygen content is plotted as a function of extracellular pH. This effect coincides with the onset of the Root effect and is caused by the adrenaline-induced increase in intracellular pH, since it disappears when the oxygen content is plotted as a function of intracellular pH. The r...