Up-regulation of acid-gated Na(+) channels (ASICs) by cystic fibrosis transmembrane conductance regulator co-expression in Xenopus oocytes.
Cystic fibrosis transmembrane conductance regulator (CFTR) functions as both a chloride channel and an epithelial transport regulator, interacting with Na(+) (epithelial sodium channel), Cl(-), renal outer medullary potassium channel(+), and H(2)O channels and some exchangers (i.e. Na(+)/H(+)) and co-transporters (Na(+)-HCO(3)(minus sign), Na(+)-K(+)-2Cl(-)). Acid-sensitive ion channels (ASICs), members of the epithelial sodium channel/degenerin superfamily, were originally cloned from neuronal tissue, and recently localized in epithelia. Because CFTR has been immunocytochemically and functionally identified in rat, murine, and human brain, the regulation of ASICs by CFTR was tested in oocytes. Our observations show that the proton-gated Na(+) current formed by the heteromultimeric ASIC1a/2a channel was up-regulated by wild type but not by Delta F508-CFTR. In contrast, the acid-gated Na(+) current associated with either the homomultimeric ASIC1a or ASIC2a channel was not influenced by wild type CFTR. The apparent equilibrium dissociation constant for extracellular Na(+) for ASIC1a/2a was increased by CFTR, but CFTR had no effect on the gating behavior or acid sensitivity of ASIC1a/2a. CFTR had no effect on the pH activation of ASIC1a/2a. We conclude that wild type CFTR elevates the acid-gated Na(+) current of ASIC1a/2a in part by altering the kinetics of extracellular Na(+) interaction.
Ji
Hong-Long
HL
Department of Physiology and Biophysics, University of Alabama, Birmingham, Alabama 35294, USA.
Jovov
Biljana
B
Fu
Jian
J
Bishop
LaToya R
LR
Mebane
Hannah C
HC
Fuller
Catherine M
CM
Stanton
Bruce A
BA
Benos
Dale J
DJ
D062565:Acid Sensing Ion Channels; D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004594:Electrophysiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D007700:Kinetics; D008564:Membrane Potentials; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins; D009865:Oocytes / Q000378:metabolism*; D011485:Protein Binding; D011522:Protons; D018075:RNA, Complementary / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation; D014981:Xenopus
C568266:ASIC1 protein, human; C112231:ASIC3 protein, human; D062565:Acid Sensing Ion Channels; C505032:CFTR protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011522:Protons; D018075:RNA, Complementary; D015222:Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012964:Sodium