{"p"=>{"__content__"=>"The epithelial sodium channel (ENaC) plays a key role in salt and water homeostasis in tetrapod vertebrates. There are four ENaC subunits (α, β, γ and δ) which form heterotrimeric αβγ- or δβγ-ENaC assemblies. ENaC activity is tightly coupled to proteolytic processing of ENaC subunits, but this effect is specific to ENaC subunit assembly and mechanistically not completely understood. Guinea pig αβγ- or δβγ-ENaCs were heterologously expressed in  oocytes and their control by extracellular proteases was investigated using protein biochemistry, two-electrode voltage-clamp and patch-clamp electrophysiology. Guinea pig αβγ-ENaC activity was tightly coupled to cleavage of its α- and γ-subunits by the endoprotease furin and extracellular chymotrypsin or trypsin. By contrast, δβγ-ENaC activity was not affected by proteases, despite cleavage of its γ-subunit by chymotrypsin. Experiments using a β-ENaC substitution, which locks ENaC in an open state after exposure to the sulfhydryl-reagent [2-(trimethylammonium)ethyl] methanethiosulfonate (MTSET), demonstrated that guinea pig δβγ-ENaCs are almost fully open when expressed in  oocytes. On-cell single-channel patch-clamp recordings confirmed that the open probability of guinea pig δβγ-ENaC is nearly 90%. These data indicate that guinea pig δβγ-ENaC is locked in an open state and thereby uncoupled from channel control by proteases.", "i"=>[{"__content__"=>"Xenopus"}, {"__content__"=>"Xenopus"}], "sub"=>[{"__content__"=>"S521C"}, {"__content__"=>"S521C"}]}}