Functional expression and CNS distribution of a beta-alanine-sensitive neuronal GABA transporter.
The synaptic action of gamma-aminobutyric acid (GABA) is terminated by high affinity, Na(+)-dependent transport processes in both neurons and glia. We have isolated a novel GABA transporter cDNA, GAT-B, which encodes a high affinity (Km = 2.3 microM), Na(+)- and Cl(-)-dependent GABA transport protein that is potently blocked by beta-alanine, a compound generally considered a selective inhibitor of glial transport. However, in situ hybridization studies indicate that GAT-B mRNA is expressed predominantly within neurons. These data indicate that the neuronal-glial distinction of GABA transporters based on inhibitor sensitivities must be reconsidered and suggest a greater diversity of GABA transporters than has been predicted by previous pharmacologic studies.
Clark
J A
JA
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
Deutch
A Y
AY
Gallipoli
P Z
PZ
Amara
S G
SG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001923:Brain Chemistry; D002352:Carrier Proteins; D002712:Chlorides / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D050485:GABA Plasma Membrane Transport Proteins; D015870:Gene Expression; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics*; D009457:Neuroglia / Q000737:chemistry; D009474:Neurons / Q000737:chemistry*; D009693:Nucleic Acid Hybridization; D027361:Organic Anion Transporters; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology; D014018:Tissue Distribution; D015091:beta-Alanine / Q000494:pharmacology*
D002352:Carrier Proteins; D002712:Chlorides; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; D015091:beta-Alanine; D004247:DNA; D012964:Sodium