Regulation of sodium channels by plunc proteins

Abstract

The present invention relates to the ability of PLUNC proteins, such as SPLUNC1 and SPLUNC2, to bind to sodium channels and inhibit activation of the sodium channels. The invention further relates to methods for regulating of sodium absorption and fluid volume and treating disorders responsive to modulating sodium absorption by modulating the binding of PLUNC proteins to sodium channels.

1 . A method of inhibiting the activation of a sodium channel, comprising contacting, a sodium channel with a PLUNC protein or a functional fragment thereof. 
     
     
         2 . The method of  claim 1 , wherein the sodium channel is an epithelial sodium channel (ENaC). 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the PLUNC protein is SPLUNC1 or SPLUNC2. 
     
     
         5 - 8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein contacting the sodium channel with a PLUNC protein comprises delivering the PLUNC protein, or a functional fragment thereof to a cell comprising the sodium channel. 
     
     
         10 . The method of  claim 1 , wherein contacting the sodium channel with a PLUNC protein comprises delivering a polynucleotide encoding the PLUNC protein or a functional fragment thereof to a cell comprising the sodium channel. 
     
     
         11 - 15 . (canceled) 
     
     
         16 . A method of increasing the volume of fluid lining an epithelial mucosal surface, comprising contacting a sodium channel present on the epithelial mucosal surface with a PLUNC protein or a functional fragment thereof. 
     
     
         17 . The method of  claim 16 , wherein the sodium channel is ENaC. 
     
     
         18 - 19 . (canceled) 
     
     
         20 . A method of treating a disorder responsive to inhibition of sodium absorption across an epithelial mucosal surface in a subject in need thereof, comprising delivering to the subject a therapeutically effective amount of a PLUNC protein or a functional fragment thereof. 
     
     
         21 . The method of  claim 20 , wherein the sodium channel is ENaC. 
     
     
         22 - 86 . (canceled)