Chloride channels in basolateral TAL membranes. XVIII. Phenylglyoxal induces functional mcCIC-Ka activity in...

Cultured mouse MTAL cells contain more mRNA encoding the Cl- channel mcCIC-Ka, which mediates CTAL Cl- absorption, than mRNA encoding the Cl- channel mmCIC-Ka, which mediates MTAL Cl- absorption. mmCIC-Ka and mcCIC-Ka have three functional differences: 1) mmCIC-Ka open time probability, Po, increases with increasing cytosolic Cl-, but variations in cytosolic Cl- do not affect Po in mcCIC-Ka; 2) mmCIC-Ka is gated by (ATP + PKA), while (ATP + PKA) have no effect on Po in mcCIC-Ka; and 3) mmCIC-Ka channels have single-ion occupancy, while mcCIC-Ka channels have multi-ion occupancy. Using basolateral vesicles from MTAL cells fused into bilayers, we evaluated the effects of 1 mM cytosolic phenylglyoxal (PGO), which binds covalently to lysine or arginine, on Cl- channels. With PGO pretreatment, Cl- channels were uniformly not gated either with increases in cytosolic-face Cl- or with (ATP + PKA) at 2 mM cytosolic-face Cl-; and they exhibited multi-ion occupancy kinetics typical for mcCIC-Ka channels. Thus, in basolateral MTAL membranes, blockade of Cl- access to arginine or lysine residues on mmCIC-Ka by PGO results in Cl- channels having the functional characteristics of mcCIC-Ka channels.