A Ca-activated nonselective cation channel (NSC) is found in principal cells of the mouse cortical collecting duct (CCD). However, the molecular identity of this channel remains unclear. We used mpkCCD cells, a mouse CCD principal cell line, to determine whether NSC represents the transient receptor potential (TRP) channel, the melastatin subfamily 4 (TRPM4). A Ca-sensitive single-channel current was observed in inside-out patches excised from the apical membrane of mpkCCD cells. Like TRPM4 channels found in other cell types, this channel has an equal permeability for Na and K and has a linear current-voltage relationship with a slope conductance of ~23 pS. The channel was inhibited by a specific TRPM4 inhibitor, 9-phenanthrol. Moreover, the frequency of observing this channel was dramatically decreased in TRPM4 knockdown mpkCCD cells. Unlike those previously reported in other cell types, the TRPM4 in mpkCCD cells was unable to be activated by hydrogen peroxide (HO). Conversely, after treatment with HO, TRPM4 density in the apical membrane of mpkCCD cells was significantly decreased. The channel in intact cell-attached patches was activated by ionomycin (a Ca ionophore), but not by ATP (a purinergic P receptor agonist). These data suggest that the NSC current previously described in CCD principal cells is actually carried through TRPM4 channels. However, the physiological role of this channel in the CCD remains to be further determined.
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| http://dx.doi.org/10.1152/ajprenal.00439.2016 | DOI Listing |
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