Role of cytosolic carbonic anhydrase Ca17a in cardiorespiratory responses to CO 2 in developing zebrafish ( Danio rerio)

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 323; no. 4; p. R532
• Main Authors: Kunert, E, Joyce, W, Pan, Y K, Chen, A, Perry, S F, Gilmour, K M
• Format: Journal Article
• Language: English
• Published: United States 01-10-2022
• Subjects: Animals; Carbon Dioxide; Carbonic Anhydrases - genetics; Gills - physiology; Hypercapnia; Hyperventilation; Mammals; RNA, Messenger; Zebrafish - physiology; heart rate; neuroepithelial cells; hypercapnia; ventilation
• ISSN: 1522-1490
• DOI: 10.1152/ajpregu.00050.2022

The sensing of environmental fluctuations and initiation of appropriate physiological responses is crucial to homeostasis. Neuroepithelial cells (NECs) in fishes are putative chemoreceptors, resembling mammalian Type I (glomus) cells, that respond in vitro to changes in O
, CO
, NH
, and pH. Cytosolic carbonic anhydrase (Ca17a) is thought to be involved in CO
sensing owing to its presence in NECs. Zebrafish (
) lacking functional Ca17a were generated via CRISPR/Cas9 technology and used to assess the role of Ca17a in initiating the cardiorespiratory responses to elevated CO
(hypercapnia). Unfortunately, the homozygous knockout mutants (
) did not survive more than ∼12-14 days postfertilization (dpf), restricting experiments to early developmental stages (4-8 dpf). Changes in ventilation (
) and cardiac (
) frequency in response to hypercapnia (1% CO
) in wild-type (
), heterozygous (
) and
fish were used to investigate Ca17a-dependent CO
sensing and downstream signaling. Wild-type fish exhibited hyperventilation during hypercapnia as indicated by an increase in
. In the
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,
fish exhibited a significantly lower resting
that became more pronounced as the fish aged. The decrease in resting
was prevented ("rescued") when
embryos were injected with
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.