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Localization and Functional Characterization of Two Na + /Monocarboxylate Transporters in zebrafish (zSMCT): electrogenic (zSMCTe/Slc5a8) and electroneutral (zSMTn/Slc5a12).
Author(s) -
PlataRamos Consuelo,
Sussman Caroline R,
Josephs Zara M,
Chang MinHwang,
Liang Jennifer O,
Romero Michael F
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1234-b
We identified and characterized the function of two different Na + /monocarboxylate cotransporters (SMCTs) from zebrafish ( Danio rerio ): electrogenic zSMCTe and electroneutral zSMCTn. Both sequences have ~50% homology to SLC5A8 (hSMCT). We characterized the physiology of both zSMCTs by functional expression in Xenopus oocytes. We recorded intracellular Na + activity ([Na + ] i ) simultaneously with membrane potential. Both zSMCTs expressed in oocytes respond to monocarboxylate (MC) addition by increasing[Na + ] i as does hSMCT. Using two electrode voltage clamp, we measured current elicited by MCs. The MC‐currents for zSMCTe are similar to hSMCT currents, yet no significant MC‐elicited current was present in zSMCTn or controls. MC‐dose response data show that zSMCTe has a lower K m for both lactate and nicotinate than zSMCTn. In situ hybridization showed that both zSMCT mRNAs are expressed in zebrafish embryos at 1, 3 and 5 days post fertilization. Both zSMCTs are expressed in the brain, eyes, swim bladder, and pronephros (kidney). However, zSMCTn is expressed in pronephric tubules (proximal) while zSMCTe is in the pronephric ducts (distal). Our data demonstrate that zSMCTe is the zebrafish ortholog of hSMCT/SLC5A8 and that zSMCTn is a novel, electroneutral form of SMCT (zSlc5a12). Our kinetic data and pronephric localization of these SMCTs suggest that zSMCTn is a low affinity, high capacity SMCT that reabsorbs the major [MCs] in proximal pronephros. zSMCTe is a high affinity SMCT implying it may used for absorbing the remaining MCs. DK56218, AHA, Wadsworth Foundation.