A single amino acid residue determines the Ca2+ permeability of AMPA-selective glutamate receptor channels.
Functional analysis of AMPA-selective glutamate receptor channels expressed in Xenopus oocytes from cloned cDNAs has shown that homomeric channels formed by the GluR1 subunit are permeable to Ca2+, whereas heteromeric channels composed of the GluR1 and GluR2 subunits show little permeability. Furthermore, substitution of glutamine for arginine in putative transmembrane segment M2 of the GluR2 subunit makes the heteromeric channels permeable to Ca2+. These results suggest that the GluR2 subunit plays a key role in keeping AMPA-selective glutamate receptor channels essentially impermeable to Ca2+ and that the critical determinant is the positively charged residue in M2 segment.
Mishina
M
M
Department of Neuropharmacology, Niigata University, Japan.
Sakimura
K
K
Mori
H
H
Kushiya
E
E
Harabayashi
M
M
Uchino
S
S
Nagahari
K
K
D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism / Q000494:pharmacology*; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D046911:Macromolecular Substances; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014981:Xenopus; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D015220:Calcium Channels; D005971:Glutamates; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid