A role for sodium-chloride cotransporters in the rapid regulation of ion uptake following acute environmental acidosis: new insights from the zebrafish model

摘要

The effects of acute exposure to acidic water on Na~+ and Cl~- homeostasis, and the mechanisms underlying their compensatory regulation, were investigated in the larval zebrafish Danio rerio. Exposure to acidic water (pH 4.0; control pH 7.6) for 2 h significantly reduced Na~+ uptake and whole body Na~+ content. Nevertheless, the capacity for Na~+ uptake was substantially increased in fish preexposed to acidic water but measured in control water. Based on the accumulation of the Na~+-selective dye, Sodium Green, two ionocyte subtypes exhibited intracellular Na~+ enrichment after preexposure to acidic water: H~+-ATPase rich (HR) cells, which coexpress the Na~+/H~+ exchanger isoform 3b (NHE3b), and a non-HR cell population. In fish experiencing Na~+-Cl~- cotransporter (NCC) knockdown, we observed no Sodium Green accumulation in the latter cell type, suggesting the non-HR cells were NCC cells. Elimination of NHE3b-expressing HR cells did not prevent the increased Na~+ uptake following acid exposure. On the other hand, the increased Na~+ uptake was abolished when the acidic water was enriched with Na~+ and Cl~-, but not with Na~+ only, indicating that the elevated Na~+ uptake after acid exposure was associated with the compensatory regulation of Cl~-. Further examinations demonstrated that acute acid exposure also reduced whole body Cl~- levels and increased the capacity for Cl~-uptake. Moreover, knockdown of NCC prevented the increased uptake of both Na~+ and Cl~- after exposure to acidic water. Together, the results of the present study revealed a novel role of NCC in the compensatory regulation of Na~+ and Cl~- uptake following acute acidosis.