Hydrogen sulfide (H2S) can act as a signaling molecule for various ion channels and/or transporters; however， little is known about its potential involvement in Ca(2+) balance. Using developing zebrafish (Danio rerio) as an in vivo model system， the present study demonstrated that acute exposure to H2S donors increased Ca(2+) influx at 4 days postfertilization， while chronic (3-day) exposure caused a rise in whole body Ca(2+) levels. The mRNA expression of Ca(2+)-transport-related genes was unaffected by H2S exposure， suggesting that posttranscriptional modifications were responsible for the altered rates of Ca(2+) uptake. Indeed， treatment of fish with the protein kinase A inhibitor H-89 abolished th... More
Hydrogen sulfide (H2S) can act as a signaling molecule for various ion channels and/or transporters; however， little is known about its potential involvement in Ca(2+) balance. Using developing zebrafish (Danio rerio) as an in vivo model system， the present study demonstrated that acute exposure to H2S donors increased Ca(2+) influx at 4 days postfertilization， while chronic (3-day) exposure caused a rise in whole body Ca(2+) levels. The mRNA expression of Ca(2+)-transport-related genes was unaffected by H2S exposure， suggesting that posttranscriptional modifications were responsible for the altered rates of Ca(2+) uptake. Indeed， treatment of fish with the protein kinase A inhibitor H-89 abolished the H2S-mediated stimulation of Ca(2+) influx， suggesting that H2S increased Ca(2+) influx by activating cAMP-protein kinase A pathways. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are two key enzymes in the endogenous synthesis of H2S. Using an antisense morpholino knockdown approach， we demonstrated that Ca(2+) influx was reduced in CBS isoform b (CBSb)- but not in CSE-deficient fish. Interestingly， the reduction in Ca(2+) influx in CBSb-deficient fish was observed only in fish that were acclimated to low-Ca(2+) water (i.e.， 25 μM Ca(2+); control: 250 μM Ca(2+)). Similarly， mRNA expression of cbsb but not cse was increased in fish acclimated to low-Ca(2+) water. Results from whole-mount immunohistochemistry further revealed that CBSb was expressed in Na(+)-K(+)-ATPase-rich cells， which are implicated in Ca(2+) uptake in zebrafish larvae. Collectively， the present study suggests a novel role for H2S in promoting Ca(2+) influx， particularly in a low-Ca(2+) environment.
