Steroids and exogenous γ-ENaC subunit modulate cation channels formed by α-ENaC in human B lymphocytes

Academic Article


  • Previous studies using whole-cell recording methods suggest that human B lymphocytes express an amiloride-sensitive, sodium-permeable channel. The present studies aim to determine whether this channel has biophysical properties and a molecular structure related to the α, β, and γ subunits of the epithelial sodium channel (ENaC). Reverse transcriptase polymerase chain reaction and Northern blots showed that human B lymphocytes express messages for both α- and β- but not γ-ENaC. Western blots showed that both α- and β- but not γ-ENaC proteins are expressed and strongly reduced by antisense oligonucleotides. Patch clamp experiments demonstrated that lymphocyte sodium channels are not active in cell-attached patches. However, membrane stretch can activate a 21-pS nonselective cation channel. The frequency of observance of this channel was significantly reduced by antisense oligonucleotide against α-ENaC but not by antisense oligonucleotide against β-ENaC, indicating that only the α subunit of ENaC is necessary to form stretch-activated cation channels. Aldosterone (1.5 μM) reduced the frequency of observance of 21-pS α-ENaC channels and simultaneously induced the appearance of spontaneously active 10-pS channels. Antisense oligonucleotide experiments showed that this 10-pS channel is formed from α- and β-ENaC. After expression of exogenous γ-ENaC, aldosterone again reduced the frequency of observance of the 21-pS α-ENaC channel but induced the appearance of a 5-pS channel, presumably a αβγ-ENaC channel. In the absence of aldosterone, the α subunit forms an α-cryptic channel that is activated by stretch, and in the presence of aldosterone, β and α subunits together form an active channel that is modulated by aldosterone.
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    Author List

  • Ma HP; Al-Khalili O; Ramosevac S; Saxena S; Liang YY; Warnock DG; Eaton DC
  • Start Page

  • 33206
  • End Page

  • 33212
  • Volume

  • 279
  • Issue

  • 32