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A Journal on Nephrology and Urology

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Minerva Urologica e Nefrologica 2003 June;55(2):131-40

language: English

Functional and molecular properties of Na+:HCO-3 cotransporters (NBC)

Soleimani M.

Department of Medicine, University of Cincinnati, Cincinnati, OH, USA and Veterans Affair Medical Center, Cincinnati, OH, USA


The so­di­um bi­car­bo­nate co­trans­port­er (NBC) is lo­cat­ed on the bas­o­lat­er­al mem­brane of the kid­ney prox­i­mal tu­bule and is re­spon­sible for the re­ab­sorp­tion of the ma­jor­ity of fil­tered bi­car­bo­nate. In se­cre­to­ry epi­the­lia (­such as pan­creat­ic ­duct) NBC is re­spon­sible for the trans­port of bi­car­bo­nate ­from the ­blood to the ­cell for the even­tu­al se­cre­tion at the ap­i­cal mem­brane. As ­such and due to its ver­sa­til­ity, NBC can func­tion in 2 dis­tinct ­modes of bi­car­bo­nate re­ab­sorp­tion or se­cre­tion de­pend­ing on the epi­the­lia. NBC is al­so ­present in a ­wide va­rie­ty of non-epi­the­lial tis­sues ­where it is main­ly in­volved ­with ­cell pH reg­u­la­tion. Recent mo­lec­u­lar clon­ing ex­peri­ments ­have iden­ti­fied the ex­is­tence of 4 NBC iso­forms (NBC1, 2, 3 and 4) and 2 NBC-re­lat­ed pro­teins AE4 and ­NCBE (anion exchanger 4 and sodium-de­pen­dent chloride-bicarbonate exchanger). Except for AE4 ­which ­does not trans­port Na, all are pre­sumed to me­di­ate the co­trans­port of Na+ and HCO3-. NBC iso­forms ­show sig­nif­i­cant ho­mol­o­gy to ­each oth­er and to the AE (an­ion ex­change) fam­i­ly. NBC1 ­shows a lim­it­ed tis­sue ex­pres­sion pat­tern, is elec­tro­gen­ic and ­plays an im­por­tant ­role in bi­car­bo­nate re­ab­sorp­tion in kid­ney prox­i­mal tu­bule. A var­i­ant of NBC1 is ex­pressed in pan­creat­ic ­duct and gas­troin­tes­ti­nal ­tract, and ­plays an im­por­tant ­role in HCO3- se­cre­tion. NBC2 and NBC3 ­have a wid­er tis­sue dis­tri­bu­tion ­than NBC1, are elec­tro­neu­tral, and are in­volved ­with ­cell pH reg­u­la­tion. The elec­tro­ge­nec­ity of NBC4 may be var­i­ant-spe­cif­ic. An NBC re­lat­ed pro­tein ­called ­NCBE me­di­ates Na-de­pen­dent, Cl-/bicarbonate ex-change. The pur­pose of ­this re­view is to sum­mar­ize func­tion­al and mo­lec­u­lar prop­er­ties of NBC iso­forms and re­lat­ed pro­teins, and dis­cuss ­their ­role and reg­u­la­tion in path­o­phy­sio­log­ic ­states.

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