A single amino acid substitution in MDEG2 specifically alters desensitization of the proton-activated cation current.
To clarify functional roles of MDEG2 (mammalian degenerin-2), a modulatory subunit of proton-activated cation channels, in MDEG1/MDEG2 heteromer, we replaced the Gly481 residue in MDEG2 with cysteine or phenylalanine and characterized them electrophysiologically. Expression of MDEG1 in Xenopus oocytes elicited proton-activated cation currents that were rapidly desensitized. Co-expression of MDEG1 and MDEG2 (or MDEG2-G481C) displayed similar current traces as MDEG1 alone. In contrast, co-expression of MDEG1 and MDEG2-G481F dramatically attenuated desensitization of the proton-activated currents. Interestingly, the G481F mutation in MDEG2 did not alter other channel properties including maximal whole-cell currents, ionic selectivity, pH-sensitivity and affinity for amiloride. Thus, Gly481 in MDEG2 specifically controls inactivation process of the MDEG1/MDEG2 channel.
Ugawa
S
S
Department of Anatomy II, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Ueda
T
T
Minami
Y
Y
Horimoto
M
M
Shimada
S
S
D062565:Acid Sensing Ion Channels; D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D003545:Cysteine / Q000235:genetics; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D005998:Glycine / Q000235:genetics / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism*; D008564:Membrane Potentials / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D010649:Phenylalanine / Q000235:genetics; D017354:Point Mutation; D011522:Protons; D051381:Rats; D014982:Xenopus laevis
D062565:Acid Sensing Ion Channels; C568425:Asic2 protein, rat; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D011522:Protons; D010649:Phenylalanine; D003545:Cysteine; D005998:Glycine