부산대학교 도서관

Kidney cells are exposed to large changes in osmolarity and hence require efficient volume regulation. Volume-regulated anion channels (VRACs) mediate regulatory volume decrease, but their expression and function in the kidney remain enigmatic. VRACs, heterohexamers of LRRC8 proteins, also conduct metabolites. This paper describes the renal expression pattern of all five LRRC8 subunits and explores their roles in mouse models. Except for vasculature-restricted LRRC8C, all LRRC8 proteins are found along the nephron. Rather than in medulla, which experiences large osmolarity changes, VRACs are most highly expressed in proximal tubules, which have metabolite-conducting LRRC8A/D channels. Targeted disruption of either subunit injures the proximal tubule and produces Fanconi-like symptoms. VRACs may mediate nonspecific exit of organic compounds in this highly transporting nephron segment.