Effect of Protamine on Ion Selectivity of Superficial and Juxtamedullary Proximal Straight Tubules

Takahashi, Mitsuo; Taniguchi, Jun; Muto, Shigeaki; Tsuruoka, Shuichi; Imai, Masashi

doi:10.1159/000045493

Cited by 5 publications

(2 citation statements)

References 21 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Measurements of relative permeabilities for Cl -. Relative permeabilities for Cl -in the isolated perfused proximal tubules were calculated from the observed transepithelial diffusion voltages according to the Goldman-Hodgkin-Katz equation, as described previously (34). Substitution of 50 mM Na + or Cl -of the control NaCl solution in the lumen by other cations or anions produced bi-ionic potentials from which the relative permeabilities were calculated.…”

Section: Methodsmentioning

confidence: 99%

Claudin-2–deficient mice are defective in the leaky and cation-selective paracellular permeability properties of renal proximal tubules

Muto¹,

Hara

Taniguchi³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

263

236

View full text Add to dashboard Cite

Claudin-2 is highly expressed in tight junctions of mouse renal proximal tubules, which possess a leaky epithelium whose unique permeability properties underlie their high rate of NaCl reabsorption. To investigate the role of claudin-2 in paracellular NaCl transport in this nephron segment, we generated knockout mice lacking claudin-2 (Cldn2 −/− ). The Cldn2 −/− mice displayed normal appearance, activity, growth, and behavior. Light microscopy revealed no gross histological abnormalities in the Cldn2 −/− kidney. Ultrathin section and freezefracture replica electron microscopy revealed that, similar to those of wild types, the proximal tubules of Cldn2 −/− mice were characterized by poorly developed tight junctions with one or two continuous tight junction strands. In contrast, studies in isolated, perfused S2 segments of proximal tubules showed that net transepithelial reabsorption of Na + , Cl -, and water was significantly decreased in Cldn2 −/− mice and that there was an increase in paracellular shunt resistance without affecting the apical or basolateral membrane resistances. Moreover, deletion of claudin-2 caused a loss of cation (Na + ) selectivity and therefore relative anion (Cl -) selectivity in the proximal tubule paracellular pathway. With free access to water and food, fractional Na + and Cl -excretions in Cldn2 −/− mice were similar to those in wild types, but both were greater in Cldn2 −/− mice after i.v. administration of 2% NaCl. We conclude that claudin-2 constitutes leaky and cation (Na + )-selective paracellular channels within tight junctions of mouse proximal tubules. mouse proximal tubule | tight junction | paracellular transport | Na/Cl transport | water transport T ight junctions (TJs) are circumferential seals around cells that selectively modulate paracellular permeability between extracellular compartments (1-3). On ultrathin-section electron microscopy, TJs appear as foci where the plasma membranes of neighboring cells make complete contact (4). On freeze-fracture electron microscopy, TJs appear as a continuous and anastomosing network of intramembranous particle strands (TJ strands) (5). These strands are mainly composed of linearly polymerized integral membrane proteins called claudins with molecular masses of ∼23 kDa (2, 3, 6). The claudin gene family contains more than 20 members in humans and in mice (2, 3, 7). The expression pattern of claudins varies considerably; most cell types express more than two claudins in various combinations to constitute mosaic TJ strands.Through the formation of TJ strands, claudins are directly involved in creating a primary barrier to the paracellular diffusion of solutes and water across epithelia (8). However, TJs are not a simple barrier: the barrier varies in tightness, measured by the transepithelial electrical resistance (R T ), and charge selectivity. Furuse et al. (9) reported that, when canine claudin-2 cDNA was transfected into high-resistance Madin-Darby canine kidney (MDCK) I cells primarily expressing claudins-1 and -4, the R T decreas...

show abstract

Section: Methodsmentioning

confidence: 99%

Claudin-2–deficient mice are defective in the leaky and cation-selective paracellular permeability properties of renal proximal tubules

Muto¹,

Hara

Taniguchi³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

263

236

View full text Add to dashboard Cite

show abstract

“…In general, paracellular electrical resistance increases along the nephron from the leaky proximal tubule [6 -7 ohms (⍀) ϫ cm 2 ] to tight collecting ducts and bladder (300,000 ⍀ ϫ cm 2 ) (21). Most segments are more permeable for cations than anions, although junctions of the superficial straight proximal tubule are anion selective (27). Although we still know little about the properties of most claudins, several groups have studied their expression profiles along the nephron with the ultimate goal of explaining transport difference among segments.…”

mentioning

confidence: 99%

Two splice variants of claudin-10 in the kidney create paracellular pores with different ion selectivities

Itallie¹,

Rogan²,

Yu³

et al. 2006

American Journal of Physiology-Renal Physiology

249

246

View full text Add to dashboard Cite

Members of the large claudin family of tight junction (TJ) proteins create the differences in paracellular conductance and charge selectivity observed among different epithelia. Previous studies demonstrated that ionic charge selectivity is influenced by acidic or basic amino acids on the first extracellular domain of claudins. We noted two alternatively spliced variants of claudin-10 in the database, 10a and 10b, which are predicted to encode two different first extracellular domains and asked whether this might be a novel mechanism to generate two different permselectivities from a single gene. Using quantitative PCR, we found that claudin-10b is widely expressed among tissues including the kidney; however, claudin-10a is unique to the kidney. Using a nondiscriminating antibody, we found that claudin-10 (a plus b) is expressed in most segments of the nephron. In situ hybridization, however, showed that mRNA for 10a is concentrated in the cortex, and mRNA for 10b is more highly expressed in the medulla. Expression in Madin-Darby canine kidney (MDCK) II and LLC-PK1 cells reveals that both variants form low-resistance pores, and that claudin-10b is more selective for cations than claudin-10a. Charge-reversing mutations of cationic residues on 10a reveal positions that contribute to its anion selectivity. We conclude that alternative splicing of claudin-10 generates unique permselectivities and might contribute to the variable paracellular transport observed along the nephron.

show abstract

Expression of an Artificial Cl? Channel in Microperfused Renal Proximal Tubules

Matsumoto

Tsuruoka

Iwamoto

et al. 2003

Journal of Membrane Biology

View full text Add to dashboard Cite

To better understand the process of fluid movement driven by Cl- conductance, a Cl- channel-forming peptide was delivered to the luminal membrane of microperfused rabbit renal proximal tubules. When the peptide (NK4-M2GlyR) was perfused, a significant new conductance was observed within 3 min and stabilized at 10 min. Alteration of the ion composition revealed it to be a Cl(-)-specific conductance. Reabsorption of Cl- (JCl) was increased by NK4-M2GlyR, but not by a scramble NK4-M2GlyR sequence, suggesting that the active peptide formed de novo Cl- channels in the luminal membrane of the perfused tubules. In the presence of the peptide, reabsorption of fluid (Jv) was dramatically increased and JNa and JCa were concomitantly increased. We propose that introduction of the new Cl- conductance in the luminal membrane leads to a coordinated efflux of water across the membrane and an increase in cation translocation via the paracellular pathway, resulting in an increase in Jv. This novel method could prove useful in characterizing mechanisms of fluid transport driven by Cl- gradients.

show abstract

Effect of Protamine on Ion Selectivity of Superficial and Juxtamedullary Proximal Straight Tubules

Cited by 5 publications

References 21 publications

Claudin-2–deficient mice are defective in the leaky and cation-selective paracellular permeability properties of renal proximal tubules

Claudin-2–deficient mice are defective in the leaky and cation-selective paracellular permeability properties of renal proximal tubules

Two splice variants of claudin-10 in the kidney create paracellular pores with different ion selectivities

Expression of an Artificial Cl? Channel in Microperfused Renal Proximal Tubules

Contact Info

Product

Resources

About