A connected tale of claudins from the renal duct to the sensory system

Claudins are tight junction membrane proteins that regulate paracellular permeability to ions and solutes in many physiological systems. The electric property of claudin is the most interesting and pertains to two important organ functions: the renal and sensorineural functions. The kidney comprises of three major segments of epithelial tubules with different paracellular permeabilities: the proximal tubule (PT), the thick acending limb of Henle’s loop (TALH) and the collecting duct (CD). Claudins act as ion channels allowing selective permeation of Na(+) in the PT, Ca(2+) and Mg(2+) in the TALH and Cl(−) in the CD. The inner ear, on the other hand, expresses claudins as a barrier to block K(+) permeation between endolymph and perilymph. The permeability properties of claudins in different organs can be attributed to claudin interaction within the cell membrane and between neighboring cells. The first extracellular loop of claudins contains determinants of paracellular ionic permeability. While analogous to transmembrane ion channels in many ways, the biophysical and biochemical properties of claudin based paracellular channels remain to be fully characterized.