Part 6 · Chapter 6.3

Paracellular Transport

Paracellular transport moves ions and water through the tight junction between adjacent cells rather than through the cell interior. In leaky epithelia (jejunum, proximal tubule), paracellular flow exceeds transcellular for Na⁺and water. Claudin composition determines both magnitude and ion selectivity of the paracellular pathway.

1. Permeability Selectivity

Claudin extracellular loops carry charged residues that line pore pathways. Cation-selective claudins (CLDN2, 10a, 15) have negatively-charged residues; anion-selective (CLDN4, 8, 17) have positively-charged. The paracellular permeability ratio P_Na/P_Cl varies from ~0.2 to ~10 depending on expressed claudin mix.

\[ J_{paracellular} \;=\; L_{TJ}\,\bigl(\Delta c + \sigma\,\Delta\Pi\bigr) + P_{ion}\,\Delta\psi \]

2. Solvent Drag

Water flow through paracellular pores entrains dissolved solutes — solvent drag. Reflection coefficient σ (0–1) measures how well the barrier excludes a solute; small solutes crossing tight junctions have low σ and are swept along with water. Paracellular solvent drag is the principal route for jejunal Na⁺, Ca²⁺, Mg²⁺absorption.

Simulation: Claudin Selectivity

Python

script.py26 lines

import numpy as np, matplotlib
matplotlib.use('Agg')
import matplotlib.pyplot as plt

# Selectivity of claudin pores: PNa/PCl ratios
claudins = ['CLDN2 (cation)','CLDN10a','CLDN15','CLDN16 (Mg2+)','CLDN4 (anion)','CLDN8']
pna_pcl = [5.0, 0.2, 3.0, 10.0, 0.3, 0.5]
cols = ['#34d399' if v > 1 else '#fbbf24' for v in pna_pcl]

fig, ax = plt.subplots(figsize=(11, 5), facecolor='#0a0f1e')
ax.set_facecolor('#111e2f'); ax.tick_params(colors='#bae6fd')
for s in ax.spines.values(): s.set_color('#334155')
ax.bar(claudins, pna_pcl, color=cols, edgecolor='#bae6fd')
ax.axhline(1, color='#f87171', ls='--', label='PNa = PCl')
ax.set_xlabel('Claudin subtype', color='#bae6fd')
ax.set_ylabel('P_Na / P_Cl', color='#bae6fd')
ax.set_yscale('log')
ax.set_title('Claudins: selective paracellular pores',
             color='#67e8f9', fontweight='bold')
ax.legend(facecolor='#1e293b', edgecolor='#334155', labelcolor='#cbd5e1')
ax.grid(True, color='#334155', alpha=0.3, axis='y', which='both')
plt.setp(ax.get_xticklabels(), rotation=20, ha='right')
plt.tight_layout()
plt.savefig('output.png', dpi=120, bbox_inches='tight', facecolor='#0a0f1e')
print('CLDN2/15 form Na+/K+ selective pores; CLDN4/8 are anion-selective')
print('CLDN16/19 mutations cause FHHNC: Mg/Ca wasting nephropathy')

Click Run to execute the Python code

Code will be executed with Python 3 on the server

3. Disease Mutations

CLDN16 / CLDN19 loss-of-function cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC): the paracellular Mg²⁺/ Ca²⁺ pore in the thick ascending limb fails. CLDN1 mutations cause neonatal ichthyosis + sclerosing cholangitis (NISCH). CLDN14 variants modulate Ca²⁺ handling and urolithiasis risk. TJ pathology is a widening clinical field.

Key References

• Van Itallie, C. M. & Anderson, J. M. (2014). “Architecture of tight junctions and principles of molecular composition.” Semin. Cell Dev. Biol., 36, 157–165.

• Yu, A. S. L. (2015). “Claudins and the kidney.” J. Am. Soc. Nephrol., 26, 11–19.

• Tamura, A. & Tsukita, S. (2014). “Paracellular barrier and channel functions of TJ claudins.” Semin. Cell Dev. Biol., 36, 177–185.

← 6.2 Transcellular 6.4 Aquaporins →