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Chloride transport in the renal proximal tubule

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Abstract

The renal proximal tubule is responsible for most of the renal sodium, chloride, and bicarbonate reabsorption. Micropuncture studies and electrophysiological techniques have furnished the bulk of our knowledge about the physiology of this tubular segment. As a consequence of the leakiness of this epithelium, paracellular ionic transport—in particular that of Cl−—is of considerable importance in this first part of the nephron. It was long accepted that proximal Cl− reabsorption proceeds solely paracellularly, but it is now known that transcellular Cl− transport also exists. Cl− channels and Cl−-coupled transporters are involved in transcellular Cl− transport. In the apical membrane, Cl−/anion (formate, oxalate and bicarbonate) exchangers represent the first step in transcellular Cl− reabsorption. A basolateral Cl−/HCO3− exchanger, involved in HCO3− reclamation, participates in the rise of intracellular Cl− activity above its equilibrium value, and thus also contributes to the creation of an outwardly directed electrochemical Cl− gradient across the cell membranes. This driving force favours Cl− diffusion from the cell to the lumen and to the interstitium. In the basolateral membrane, the main mechanism for transcellular Cl− reabsorption is a Cl− conductance, but a Na+-driven Cl−/HCO3− exchanger may also participate in Cl− reabsorption.

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Notes

  1. As a consequence, an electrical event induced experimentally at the BL membrane (for example, a change in the basolateral membrane potential, consecutive to a peritubular ionic substitution) may not be a reliable reflection of the current flowing across the BL membrane resistance, because of the distortion induced by part of current flowing across the other conductive barriers of the epithelium. For the theoretical development of electrical equivalent circuit of PT epithelium, the reader is referred to [7, 8, 14, 79].

  2. The shunt pathway of PT is largely selective for Cl− [7, 9, 86].

  3. It is interesting to note that the resistance values reported for the mammals are lower than those measured in amphibian: for example, the much lower shunt resistance in rat PT than in Necturus PT [15, 36] infers that for the same VTE, the paracellular current flow, and hence paracellular ionic transport, will be higher in the rat than in Necturus.

  4. In the early portion of PT, the favourable driving force for transepithelial Cl− absorption is provided by the lumen-negative potential, and in the later PT by the transtubular Cl− concentration gradient.

  5. In the text, “uphill” transport indicates the transmembrane transport of an ion against its electrochemical potential difference, as opposed to “downhill” transport (down the electrochemical potential difference).

  6. The presence of Cl−/formate (or Cl−/oxalate) exchange has not been addressed specifically in the amphibian PT. Indirect evidence indicates that the presence of such transport mechanism is unlikely: luminal DIDS increases αCl [1], which is the opposite effect of that expected in the case of a DIDS-sensitive apical Cl− influx.

  7. Anionic substitutions for Cl− may change cell membrane conductances other than GCl. This will result in differences between the permeability sequence of the membrane (established by measuring ΔVBL induced by various substitutive anions) and the conductance sequence of the membrane (established by testing the contribution of GCl to the global conductance of the membrane under the various experimental conditions represented by anionic substitution). For example, in Necturus PT, the permeability sequence for halide ions is F−>Cl−>Br−>I−, which is included in the Eisenman’s predicted sequence [35], and the membrane was more permeable to SCN−, ClO4− and NO3− than to Cl−. The membrane conductance sequence is: Cl−≈BrO3−<Br−≤ClO3−<I−≈F−<NO3−<ClO4−<SCN− [10].

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Acknowledgements

I acknowledge S.R. Thomas for helpful discussion, and A. Edelman and J. Teulon for their encouragement.

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  1. Inserm U 467, Faculté de Médecine Necker-Enfants-Malades, Université Paris V, 156 rue de Vaugirard, 75730, Paris Cedex 15, France

    Gabrielle Planelles

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Correspondence to Gabrielle Planelles.

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This review is dedicated to Takis Anagnostopoulos, in memoriam.

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Planelles, G. Chloride transport in the renal proximal tubule. Pflugers Arch - Eur J Physiol 448, 561–570 (2004). https://doi.org/10.1007/s00424-004-1309-y

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  • DOI: https://doi.org/10.1007/s00424-004-1309-y

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