PMID- 10187795
OWN - NLM
STAT- MEDLINE
DCOM- 19990503
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 15
DP  - 1999 Apr 9
TI  - The pre-transmembrane 1 domain of acid-sensing ion channels participates in the
      ion pore.
PG  - 10129-32
AB  - The acid-sensing ion channel (ASIC) subunits ASIC1, ASIC2, and ASIC3 are members 
      of the amiloride-sensitive Na+ channel/degenerin family of ion channels. They
      form proton-gated channels that are expressed in the central nervous system and
      in sensory neurons, where they are thought to play an important role in pain
      accompanying tissue acidosis. A splice variant of ASIC2, ASIC2b, is not active on
      its own but modifies the properties of ASIC3. In particular, whereas most members
      of the amiloride-sensitive Na+ channel/degenerin family are highly selective for 
      Na+ over K+, ASIC3/ASIC2b heteromultimers show a nonselective component. Chimeras
      of the two splice variants allowed identification of a 9-amino acid region
      preceding the first transmembrane (TM) domain (pre-TM1) of ASIC2 that is involved
      in ion permeation and is critical for Na+ selectivity. Three amino acids in this 
      region (Ile-19, Phe-20, and Thr-25) appear to be particularly important, because 
      channels mutated at these residues discriminate poorly between Na+ and K+. In
      addition, the pH dependences of the activity of the F20S and T25K mutants are
      changed as compared with that of wild-type ASIC2. A corresponding ASIC3 mutant
      (T26K) also has modified Na+ selectivity. Our results suggest that the pre-TM1
      region of ASICs participates in the ion pore.
FAU - Coscoy, S
AU  - Coscoy S
AD  - Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la
      Recherche Scientifique-UPR 411, 660 route des Lucioles, Sophia Antipolis, 06560
      Valbonne, France.
FAU - de Weille, J R
AU  - de Weille JR
FAU - Lingueglia, E
AU  - Lingueglia E
FAU - Lazdunski, M
AU  - Lazdunski M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Degenerin Sodium Channels)
RN  - 0 (Epithelial Sodium Channels)
RN  - 0 (Ion Channels)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Potassium Channels)
RN  - 0 (Sodium Channels)
SB  - IM
MH  - Alternative Splicing
MH  - Amino Acid Sequence
MH  - Animals
MH  - COS Cells
MH  - Degenerin Sodium Channels
MH  - Electrophysiology
MH  - Epithelial Sodium Channels
MH  - Ion Channels/*chemistry/genetics/metabolism
MH  - Molecular Sequence Data
MH  - Nerve Tissue Proteins/*chemistry/genetics/metabolism
MH  - Potassium Channels/*chemistry/genetics/metabolism
MH  - Sodium Channels/*chemistry/genetics/metabolism
EDAT- 1999/04/03 00:00
MHDA- 1999/04/03 00:01
CRDT- 1999/04/03 00:00
PHST- 1999/04/03 00:00 [pubmed]
PHST- 1999/04/03 00:01 [medline]
PHST- 1999/04/03 00:00 [entrez]
AID - 10.1074/jbc.274.15.10129 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 9;274(15):10129-32. doi: 10.1074/jbc.274.15.10129.