Aim: 

The DEG/ENaC protein family comprises voltage-independent, amiloride-sensitive cation channels. It includes acid sensing ion channels (ASICs), involved in various functions in the nervous system and epithelial sodium channels (ENaCs), key players in sodium transport across epithelia. 'Classical' ENaCs are formed by three different subunits: a, b and g. A forth subunit, d, has been found in humans and primates. It associates with ENaC b and g to form channels but it is mainly expressed in non-epithelial tissues such as the nervous system. Several lines of evidence suggest that DEG/ENaC subunits may interact promiscuously to form heteromeric ion channels with diverse biophysical properties. Thus, d could modulate abg channels or form channels with other DEG/ENaC subunits in tissues where a, b or g are not expressed. ASICs have been proposed to interact with ENaC subunits to form heteromeric ion channels and also to directly modulate other ion channels such as BK. We are assessing the physiological relevance of these interactions, by verifying subunits co-expression in native tissues; quantifying the efficiency of subunits interaction; biophysically characterizing the different subunit assemblies.

Methods: membrane expression of fluorescently-tagged DEG/ENaC subunits in Xenopus oocytes and Two Electrode Voltage Clamp.

Results and Discussion: 

Our results compare the efficiency of interactions between various ENaC/DEG subunits, showing that d is less efficient than a to form channels with b and g subunits. The significance and physiological relevance of the different ENaC/DEG combinations will be discussed.