title: Glycosphingolipids modulate renal phosphate transport in potassium deficiency.
abstract: BACKGROUND
  Potassium (K) deficiency (KD) and/or hypokalemia have been associated with disturbances of phosphate metabolism. The purpose of the present study was to determine the cellular mechanisms that mediate the impairment of renal proximal tubular Na/Pi cotransport in a model of K deficiency in the rat.
  
  
  METHODS
  K deficiency in the rat was achieved by feeding rats a K-deficient diet for seven days, which resulted in a marked decrease in serum and tissue K content.
  
  
  RESULTS
  K deficiency resulted in a marked increase in urinary Pi excretion and a decrease in the V(max) of brush-border membrane (BBM) Na/Pi cotransport activity (1943 +/- 95 in control vs. 1184 +/- 99 pmol/5 sec/mg BBM protein in K deficiency, P < 0.02). Surprisingly, the decrease in Na/Pi cotransport activity was associated with increases in the abundance of type I (NaPi-1), and type II (NaPi-2) and type III (Glvr-1) Na/Pi protein. The decrease in Na/Pi transport was associated with significant alterations in BBM lipid composition, including increases in sphingomyelin, glucosylceramide, and ganglioside GM3 content and a decrease in BBM lipid fluidity. Inhibition of glucosylceramide synthesis resulted in increases in BBM Na/Pi cotransport activity in control and K-deficient rats. The resultant Na/Pi cotransport activity in K-deficient rats was the same as in control rats (1148 +/- 52 in control + PDMP vs. 1152 +/- 61 pmol/5 sec/mg BBM protein in K deficiency + PDMP). These changes in transport activity occurred independent of further changes in BBM NaPi-2 protein or renal cortical NaPi-2 mRNA abundance.
  
  
  CONCLUSIONS
  K deficiency in the rat causes inhibition of renal Na/Pi cotransport activity by post-translational mechanisms that are mediated in part through alterations in glucosylceramide content and membrane lipid dynamics.
authors.affiliation: Department of Internal Medicine, The University of Texas Southwestern Medical Center and VA Medical Center, Dallas, Texas 75216, USA.
authors.forename: H K
authors.initials: HK
authors.lastname: Zajicek
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Puttaparthi
authors.forename: N
authors.initials: N
authors.lastname: Halaihel
authors.forename: D
authors.initials: D
authors.lastname: Markovich
authors.forename: J
authors.initials: J
authors.lastname: Shayman
authors.forename: R
authors.initials: R
authors.lastname: Béliveau
authors.forename: P
authors.initials: P
authors.lastname: Wilson
authors.forename: T
authors.initials: T
authors.lastname: Rogers
authors.forename: M
authors.initials: M
authors.lastname: Levi
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005679:G(M3) Ganglioside / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D005963:Glucosylceramides / Q000378:metabolism*; D007008:Hypokalemia / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008560:Membrane Fluidity / Q000502:physiology*; D008871:Microvilli / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D010758:Phosphorus / Q000652:urine; D011191:Potassium Deficiency / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D027981:Symporters; D014982:Xenopus laevis
chemical_list: D002352:Carrier Proteins; D005679:G(M3) Ganglioside; D005963:Glucosylceramides; D010710:Phosphates; D012333:RNA, Messenger; D011991:Receptors, Virus; C493588:Slc20a1 protein, rat; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D027981:Symporters; C067981:leukemia virus receptor, gibbon ape; D010758:Phosphorus