Chloride Channels in Basolateral TAL Membranes. XVIII. Phenylglyoxal Induces Functional mcClC-Ka Activity in Basolateral MTAL Membranes

Cultured mouse MTAL cells contain more mRNA encoding the Cl- channel mcClC-Ka, which mediates CTAL Cl- absorption, than mRNA encoding the Cl- channel mmClC-Ka, which mediates MTAL Cl- absorption. mmClC-Ka and mcClC-Ka have three functional differences: 1) mmClC-Ka open time probability, P o, increases with increasing cytosolic Cl-, but variations in cytosolic Cl- do not affect P o in mcClC-Ka; 2) mmClC-Ka is gated by (ATP + PKA), while (ATP + PKA) have no effect on P o in mcClC-Ka; and 3) mmClC-Ka channels have single-ion occupancy, while mcClC-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 mcClC-Ka channels. Thus, in basolateral MTAL membranes, blockade of Cl- access to arginine or lysine residues on mmClC-Ka by PGO results in Cl- channels having the functional characteristics of mcClC-Ka channels.