PUBLICATION

The role of cytosolic carbonic anhydrase Ca17a in cardiorespiratory responses to CO2 in developing zebrafish (Danio rerio)

Authors
Kunert, E., Joyce, W., Pan, Y.K., Chen, A., Perry, S.F., Gilmour, K.M.
ID
ZDB-PUB-220824-19
Date
2022
Source
American journal of physiology. Regulatory, integrative and comparative physiology   323(4): R532-R546 (Journal)
Registered Authors
Joyce, William, Kunert, Emma, Perry, Steve F.
Keywords
heart rate, hypercapnia, neuroepithelial cells, ventilation
MeSH Terms
  • Animals
  • Carbon Dioxide
  • Carbonic Anhydrases*/genetics
  • Gills/physiology
  • Hypercapnia
  • Hyperventilation
  • Mammals
  • RNA, Messenger
  • Zebrafish*/physiology
PubMed
35993559 Full text @ Am. J. Physiol. Regul. Integr. Comp. Physiol.
Abstract
The sensing of environmental fluctuations and initiation of appropriate physiological responses is crucial to homeostasis. Neuroepithelial cells (NECs) in fishes are putative chemoreceptors that respond in vitro to changes in O2, CO2, NH3 and pH. Cytosolic carbonic anhydrase (Ca17a) is thought to be involved in CO2 sensing owing to its presence in NECs. Zebrafish (Danio rerio) lacking functional Ca17a were generated via CRISPR/Cas9 technology and used to assess the role of Ca17a in initiating the cardiorespiratory responses to elevated CO2 (hypercapnia). Unfortunately, the homozygous knockout mutants (ca17a-/-) did not survive longer than ~12-14 days post fertilization (dpf), restricting experiments to early developmental stages (4-8 dpf). Changes in ventilation (fV) and cardiac (fH) frequency in response to hypercapnia (1% CO2) in wild-type (ca17a+/+), heterozygous (ca17a+/-) and ca17a-/- fish were used to investigate Ca17a-dependent CO2 sensing and downstream signalling. Wild-type fish exhibited hyperventilation during hypercapnia as indicated by an increase in fV. In the ca17a-/- fish, the hyperventilatory response was attenuated markedly, but only at 8 dpf. Hypercapnic tachycardia was observed for all genotypes and did not appear to be influenced by the absence of Ca17a. Interestingly, ca17a-/- fish exhibited a significantly lower resting fH- that became more pronounced as the fish aged. The decrease in resting fH was prevented ("rescued") when ca17a-/- embryos were injected with ca17a mRNA. Collectively, the results of this study support a role for Ca17a in promoting hyperventilation during hypercapnia in larval zebrafish and suggest a previously unrecognized role for Ca17a in determining resting heart rate.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping