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Purinergic Regulation of Amiloride‐Sensitive Lung Sodium Channels
Author(s) -
Bao HuiFang,
Chen XiJuan,
Jain Lucky,
Eaton Douglas C
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a549
Subject(s) - amiloride , ppads , purinergic receptor , microbiology and biotechnology , sodium channel , chemistry , autocrine signalling , epithelial sodium channel , biophysics , sodium , receptor , ion transporter , biology , biochemistry , membrane , organic chemistry
ATP is known to regulate ion transport in a variety of epithelia by stimulating P2 purinoreceptors. Since ATP, as an autocrine regulator, can be released by lung epithelial cells, we used alveolar type II (AT2) cells, which were isolated from rat lungs and grown in primary culture, as a model to investigate how ATP regulates sodium transport in lung epithelia. Two types of amiloride‐sensitive channels were characterized in cell‐attached patches formed on the apical membrane of the cells. One was a 6‐pS highly selective channel (HSC) while the other was a 21‐pS non‐selective channel (NSC). Application of 100 μM ATP to the cells strongly inhibited HSC activity by reducing the open probability (P o ), with an IC50 of 15 μM, but not the channel density or conductance. Conversely, ATP addition significantly increased the P o of NSC. The effects of ATP on both HSC and NSC were blocked by either PPADS (P2 receptor antagonist) or XAMR (P2Y 2 receptor antagonist). ATP inhibition of HSC was mimicked by 100 μM UTP. PPADS or XAMR alone resulted in an increase in the P o of HSC, indicating that the channel is constitutively inhibited via an autocrine mechanism associated with releasing of endogenous ATP. These results suggest that sodium transport across lung epithelia can be regulated by P2 purinoreceptors. Since HSC is specific for sodium transport, further determination of the pathways for the differential regulation of HSSC and NSC induced by P2 purinoreceptor may provide novel information on the complexity of sodium transport that is either reduced or increased in lung diseases.