skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


  • NSF Public Access
  • Search Results
  • Adrenergically induced translocation of red blood cell β-adrenergic sodium-proton exchangers has ecological relevance for hypoxic and hypercapnic white seabass
Title: Adrenergically induced translocation of red blood cell β-adrenergic sodium-proton exchangers has ecological relevance for hypoxic and hypercapnic white seabass
White seabass ( Atractoscion nobilis) increasingly experience periods of low oxygen (O 2 ; hypoxia) and high carbon dioxide (CO 2 , hypercapnia) due to climate change and eutrophication of the coastal waters of California. Hemoglobin (Hb) is the principal O 2 carrier in the blood and in many teleost fishes Hb-O 2 binding is compromised at low pH; however, the red blood cells (RBC) of some species regulate intracellular pH with adrenergically stimulated sodium-proton-exchangers (β-NHEs). We hypothesized that RBC β-NHEs in white seabass are an important mechanism that can protect the blood O 2 -carrying capacity during hypoxia and hypercapnia. We determined the O 2 -binding characteristics of white seabass blood, the cellular and subcellular response of RBCs to adrenergic stimulation, and quantified the protective effect of β-NHE activity on Hb-O 2 saturation. White seabass had typical teleost Hb characteristics, with a moderate O 2 affinity (Po 2 at half-saturation; P 50 2.9 kPa) that was highly pH-sensitive (Bohr coefficient −0.92; Root effect 52%). Novel findings from super-resolution microscopy revealed β-NHE protein in vesicle-like structures and its translocation into the membrane after adrenergic stimulation. Microscopy data were corroborated by molecular and phylogenetic results and a functional characterization of β-NHE activity. The activation of RBC β-NHEs increased Hb-O 2 saturation by ∼8% in normoxic hypercapnia and by up to ∼20% in hypoxic normocapnia. Our results provide novel insight into the cellular mechanism of adrenergic RBC stimulation within an ecologically relevant context. β-NHE activity in white seabass has great potential to protect arterial O 2 transport during hypoxia and hypercapnia but is less effective during combinations of these stressors.  more » « less
Award ID(s):
1754994
PAR ID:
10322220
Author(s) / Creator(s):
; ;
Date Published:
Journal Name:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Volume:
321
Issue:
5
ISSN:
0363-6119
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; (, Journal of Experimental Biology)
    null (Ed.)
    ABSTRACT Oxygen (O2) and carbon dioxide (CO2) transport are tightly coupled in many fishes as a result of the presence of Root effect hemoglobins (Hb), whereby reduced pH reduces O2 binding even at high O2 tensions. Red blood cell carbonic anhydrase (RBC CA) activity limits the rate of intracellular acidification, yet its role in O2 delivery has been downplayed. We developed an in vitro assay to manipulate RBC CA activity while measuring Hb-O2 offloading following a physiologically relevant CO2-induced acidification. RBC CA activity in red drum (Sciaenops ocellatus) was inhibited with ethoxzolamide by 53.7±0.5%, which prompted a significant reduction in O2 offloading rate by 54.3±5.4% (P=0.0206, two-tailed paired t-test; n=7). Conversely, a 2.03-fold increase in RBC CA activity prompted a 2.14-fold increase in O2 offloading rate (P<0.001, two-tailed paired t-test; n=8). This approximately 1:1 relationship between RBC CA activity and Hb-O2 offloading rate coincided with a similar allometric scaling exponent for RBC CA activity and maximum metabolic rate. Together, our data suggest that RBC CA is rate limiting for O2 delivery in red drum. 
    more » « less
  2. ; ; ; ; ; ; ; ; (, BMC Biology)
    Abstract BackgroundComplex organismal traits are often the result of multiple interacting genes and sub-organismal phenotypes, but how these interactions shape the evolutionary trajectories of adaptive traits is poorly understood. We examined how functional interactions between cardiorespiratory traits contribute to adaptive increases in the capacity for aerobic thermogenesis (maximal O2consumption,V̇O2max, during acute cold exposure) in high-altitude deer mice (Peromyscus maniculatus). We crossed highland and lowland deer mice to produce F2inter-population hybrids, which expressed genetically based variation in hemoglobin (Hb) O2affinity on a mixed genetic background. We then combined physiological experiments and mathematical modeling of the O2transport pathway to examine the links between cardiorespiratory traits andV̇O2max. ResultsPhysiological experiments revealed that increases in Hb-O2affinity of red blood cells improved blood oxygenation in hypoxia but were not associated with an enhancement inV̇O2max. Sensitivity analyses performed using mathematical modeling showed that the influence of Hb-O2affinity onV̇O2max in hypoxia was contingent on the capacity for O2diffusion in active tissues. ConclusionsThese results suggest that increases in Hb-O2affinity would only have adaptive value in hypoxic conditions if concurrent with or preceded by increases in tissue O2diffusing capacity. In high-altitude deer mice, the adaptive benefit of increasing Hb-O2affinity is contingent on the capacity to extract O2from the blood, which helps resolve controversies about the general role of hemoglobin function in hypoxia tolerance. 
    more » « less
  3. ; ; (, Journal of Experimental Biology)
    ABSTRACT The gill is the primary site of ionoregulation and gas exchange in adult teleost fishes. However, those characteristics that benefit diffusive gas exchange (large, thin gills) may also enhance the passive equilibration of ions and water that threaten osmotic homeostasis. Our literature review revealed that gill surface area and thickness were similar in freshwater (FW) and seawater (SW) species; however, the diffusive oxygen (O2) conductance (Gd) of the gill was lower in FW species. While a lower Gd may reduce ion losses, it also limits O2 uptake capacity and possibly aerobic performance in situations of high O2 demand (e.g. exercise) or low O2 availability (e.g. environmental hypoxia). We also found that FW fishes had significantly higher haemoglobin (Hb)–O2 binding affinities than SW species, which will increase the O2 diffusion gradient across the gills. Therefore, we hypothesized that the higher Hb–O2 affinity of FW fishes compensates, in part, for their lower Gd. Using a combined literature review and modelling approach, our results show that a higher Hb–O2 affinity in FW fishes increases the flux of O2 across their low-Gd gills. In addition, FW and SW teleosts can achieve similar maximal rates of O2 consumption (ṀO2,max) and hypoxia tolerance (Pcrit) through different combinations of Hb–O2 affinity and Gd. Our combined data identified novel patterns in gill and Hb characteristics between FW and SW fishes and our modelling approach provides mechanistic insight into the relationship between aerobic performance and species distribution ranges, generating novel hypotheses at the intersection of cardiorespiratory and ionoregulatory fish physiology. 
    more » « less
  4. ; ; ; ; ; (, Biology Letters)
    Animals developing at high elevation experience a suite of environmental challenges, most notably the low partial pressure of oxygen ( P O 2 ) in ambient air. In low P O 2 , bird species with high-elevation ancestry consistently demonstrate higher hatching success than lowland counterparts, suggesting highland birds are adapted to restricted O 2 (hypoxia) in early development. Haemoglobin (Hb), the critical oxygen-transport protein, is a likely target of P O 2 -related selection across ontogeny since Hb isoforms expressed at distinct developmental stages demonstrate different O 2 affinities. To test if Hb function is under P O 2 -related selection at different ontogenetic stages, we sampled a songbird, the hooded siskin ( Spinus magellanicus ), across two approximately 4000 m elevational transects. We sequenced all of the loci that encode avian Hb isoforms, and tested for signatures of spatially varying selection by comparing divergence patterns in Hb loci to other loci sampled across the genome. We found strong signatures of diversifying selection at non-synonymous sites in loci that contribute to embryonic ( α π , β H ) and definitive ( β A ) Hb isoforms. This is the first evidence for selection on embryonic haemoglobin in high-elevation Neoaves. We conclude that selection on Hb function at brief, but critical stages of ontogeny may be a vital component to high elevation adaptation in birds. 
    more » « less
  5. ; ; ; ; ; ; ; ; ; ; et al (, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology)
    Hemoglobins (Hbs) of crocodilians are reportedly characterized by unique mechanisms of allosteric regulatory control, but there are conflicting reports regarding the importance of different effectors, such as chloride ions, organic phosphates, and CO 2 . Progress in understanding the unusual properties of crocodilian Hbs has also been hindered by a dearth of structural information. Here, we present the first comparative analysis of blood properties and Hb structure and function in a phylogenetically diverse set of crocodilian species. We examine mechanisms of allosteric regulation in the Hbs of 13 crocodilian species belonging to the families Crocodylidae and Alligatoridae. We also report new amino acid sequences for the α- and β-globins of these taxa, which, in combination with structural analyses, provide insights into molecular mechanisms of allosteric regulation. All crocodilian Hbs exhibited a remarkably strong sensitivity to CO 2 , which would permit effective O 2 unloading to tissues in response to an increase in metabolism during intense activity and diving. Although the Hbs of all crocodilians exhibit similar intrinsic O 2 -affinities, there is considerable variation in sensitivity to Cl − ions and ATP, which appears to be at least partly attributable to variation in the extent of NH 2 -terminal acetylation. Whereas chloride appears to be a potent allosteric effector of all crocodile Hbs, ATP has a strong, chloride-independent effect on Hb-O 2 affinity only in caimans. Modeling suggests that allosteric ATP binding has a somewhat different structural basis in crocodilian and mammalian Hbs. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email