Fluid transport and ion fluxes in mammalian kidney proximal tubule: a model analysis of isotonic transport

TY - JOUR

T1 - Fluid transport and ion fluxes in mammalian kidney proximal tubule: a model analysis of isotonic transport

AU - Larsen, Erik Hviid

AU - Møbjerg, N.

AU - Sørensen, J. N.

N1 - KEYWORDS epithelial fluid transport • leaky epithelia • mammalian proximal tubule • mathematical model • Na+ recirculation theory • solute coupled water transport

PY - 2006

Y1 - 2006

N2 - Aim: By mathematical modelling, we analyse conditions for near-isotonic and isotonic transport by mammalian kidney proximal tubule.Methods: The model comprises compliant lateral intercellular space (lis) and cells, and infinitely large luminal and peritubular compartments with diffusible species: Na+, K+, Cl- and an intracellular non-diffusible anion. Unknown model variables are solute concentrations, electrical potentials, volumes and hydrostatic pressures in cell and lis, and transepithelial potential. We used data mainly from rat proximal tubule to model epithelial cells and interspace with luminal and peritubular baths of identical composition.Results: The model of the tubular epithelium with physiological water permeability and paracellular electrical resistance generates solute coupled water uptake with an approx. 3% hypertonic absorbate. This function remains unperturbed following 'blocking' of apical water channels and in 'aquaporin-null' simulation. Reduced rate of volume reabsorption in AQP(-/-) mice would also require decreased apical sodium permeability. Paracellular convection accounts for approx. 36% of the net Na+ absorption, and the model epithelium accomplishes uphill water transport similar to rat proximal tubule. Na+ recirculation is required for truly isotonic transport. The tonicity of the absorbate and the recirculation flux depend critically on ion permeabilities of interspace basement membrane.Conclusion: Our model based on solute-solvent coupling in lateral space simulates major physiological features of proximal tubule, including significantly lower water permeability of the AQP1-null preparation, and a ratio of net sodium uptake and oxygen consumption exceeding that predicted from stoichiometry of the Na+/K+-pump. Physical properties of interspace basement membrane are critical for obtaining near-isotonic and truly isotonic transport.

AB - Aim: By mathematical modelling, we analyse conditions for near-isotonic and isotonic transport by mammalian kidney proximal tubule.Methods: The model comprises compliant lateral intercellular space (lis) and cells, and infinitely large luminal and peritubular compartments with diffusible species: Na+, K+, Cl- and an intracellular non-diffusible anion. Unknown model variables are solute concentrations, electrical potentials, volumes and hydrostatic pressures in cell and lis, and transepithelial potential. We used data mainly from rat proximal tubule to model epithelial cells and interspace with luminal and peritubular baths of identical composition.Results: The model of the tubular epithelium with physiological water permeability and paracellular electrical resistance generates solute coupled water uptake with an approx. 3% hypertonic absorbate. This function remains unperturbed following 'blocking' of apical water channels and in 'aquaporin-null' simulation. Reduced rate of volume reabsorption in AQP(-/-) mice would also require decreased apical sodium permeability. Paracellular convection accounts for approx. 36% of the net Na+ absorption, and the model epithelium accomplishes uphill water transport similar to rat proximal tubule. Na+ recirculation is required for truly isotonic transport. The tonicity of the absorbate and the recirculation flux depend critically on ion permeabilities of interspace basement membrane.Conclusion: Our model based on solute-solvent coupling in lateral space simulates major physiological features of proximal tubule, including significantly lower water permeability of the AQP1-null preparation, and a ratio of net sodium uptake and oxygen consumption exceeding that predicted from stoichiometry of the Na+/K+-pump. Physical properties of interspace basement membrane are critical for obtaining near-isotonic and truly isotonic transport.

U2 - 10.1111/j.1748-1716.2006.01580.x

DO - 10.1111/j.1748-1716.2006.01580.x

M3 - Journal article

C2 - 16734754

SN - 1748-1708

VL - 187

SP - 177

EP - 189

JO - Acta Physiologica (Print Edition)

JF - Acta Physiologica (Print Edition)

IS - 1-2

ER -