A calcium-permeable non-selective cation channel in the thick ascending limb apical membrane of the mouse kidney

Non-selective cation channels have been described in the basolateral membrane of the renal tubule, but little is known about functional channels on the apical side. Apical membranes of microdissected fragments of mouse cortical thick ascending limbs were searched for ion channels using the cell-free configuration of the patch-clamp technique. A cation channel with a linear current–voltage relationship (19pS) that was permeable both to monovalent cations [PNH4(1.7)>PNa (1.0)=PK (1.0)] and to Ca2+ (PCa/PNa≈0.3) was detected. Unlike the basolateral TRPM4 Ca2+-impermeable non-selective cation channel, this non-selective cation channel was insensitive to internal Ca2+, pH and ATP. The channel was already active after patch excision, and its activity increased after reduced pressure was applied via the pipette. External gadolinium (10−5M) decreased the channel-open probability by 70% in outside-out patches, whereas external amiloride (10−4M) had no effect. Internal flufenamic acid (10−4M) inhibited the channel in inside-out patches. Its properties suggest that the current might be supported by the TRPM7 protein that is expressed in the loop of Henle. The conduction properties of the channel suggest that it could be involved in Ca2+ signaling. ► A cation channel is present in the apical membrane of the loop of Henle in mouse. ► The channel is permeable to divalent and monovalent cations like the TRPM7 channel. ► The channel provides a trans-cellular pathway for calcium in the loop of Henle.