Hydrogen sulfide inhibits Na+ uptake in larval zebrafish, Danio rerio

Pflugers Arch. 2015 Apr;467(4):651-64. doi: 10.1007/s00424-014-1550-y. Epub 2014 Jun 18.


The present study investigated the role of hydrogen sulfide (H2S) in regulating Na(+) uptake in larval zebrafish, Danio rerio. Waterborne treatment of larvae at 4 days post-fertilization (dpf) with Na2S or GYY-4137 (chemicals known to generate H2S) significantly reduced Na(+) uptake. Exposure of larvae to water enriched with NaCl (1 mM NaCl) caused a pronounced reduction in Na(+) uptake which was prevented by pharmacological inhibition of cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE), two key enzymes involved in the endogenous synthesis of H2S. Furthermore, translational gene knockdown of CSE and CBSb significantly increased the basal rate of Na(+) uptake. Waterborne treatment with Na2S significantly decreased whole-body acid excretion and reduced Na(+) uptake in larval zebrafish preexposed to acidic (pH 4.0) water (a condition shown to promote Na(+) uptake via Na(+)-H(+)-exchanger 3b, NHE3b). However, Na2S did not affect Na(+) uptake in larvae depleted of NHE3b-containing ionocytes (HR cells) after knockdown of transcription factor glial cell missing 2 (gcm2) in which Na(+) uptake occurs predominantly via Na(+)-Cl(-) co-transporter (NCC)-containing cells. These observations suggest that Na(+) uptake via NHE3b, but not NCC, is regulated by H2S. Whole-mount immunohistochemistry demonstrated that ionocytes expressing NHE3b also express CSE. These data suggests a physiologically relevant role of H2S as a mechanism to lower Na(+) uptake in zebrafish larvae, probably through its inhibitory action on NHE3b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cystathionine beta-Synthase / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Hydrogen Sulfide / pharmacology*
  • Larva / drug effects
  • Larva / metabolism
  • Lyases / antagonists & inhibitors
  • Lyases / genetics
  • Lyases / metabolism
  • Skin Absorption*
  • Sodium / metabolism*
  • Sodium Chloride Symporters / metabolism
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers / genetics
  • Sodium-Hydrogen Exchangers / metabolism
  • Sulfites / pharmacology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism


  • DNA-Binding Proteins
  • Sodium Chloride Symporters
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers
  • Sulfites
  • Transcription Factors
  • Zebrafish Proteins
  • gcm2 protein, zebrafish
  • Sodium
  • Lyases
  • Cystathionine beta-Synthase
  • cystathionine beta-lyase
  • sodium sulfite
  • Hydrogen Sulfide