PMID- 10358010
OWN - NLM
STAT- MEDLINE
DCOM- 19990706
LR  - 20191210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 24
DP  - 1999 Jun 11
TI  - Functional characterization of the Betaine/gamma-aminobutyric acid transporter
      BGT-1 expressed in Xenopus oocytes.
PG  - 16709-16
AB  - Betaine is an osmolyte accumulated in cells during osmotic cell shrinkage. The
      canine transporter mediating cellular accumulation of the osmolyte betaine and
      the neurotransmitter gamma-aminobutyric acid (BGT-1) was expressed in Xenopus
      oocytes and analyzed by two-electrode voltage clamp and tracer flux studies.
      Exposure of oocytes expressing BGT-1 to betaine or gamma-aminobutyric acid (GABA)
      depolarized the cell membrane in the current clamp mode and induced an inward
      current under voltage clamp conditions. At 1 mM substrate the induced currents
      decreased in the following order: betaine = GABA > diaminobutyric acid =
      beta-alanine > proline = quinidine > dimethylglycine > glycine > sarcosine. Both 
      the Vmax and Km of GABA- and betaine-induced currents were voltage-dependent, and
      GABA- and betaine-induced currents and radioactive tracer uptake were strictly
      Na+-dependent but only partially dependent on the presence of Cl-. The apparent
      affinity of GABA decreased with decreasing Na+ concentrations. The Km of Na+ also
      depended on the GABA and Cl- concentration. A decrease of the Cl- concentration
      reduced the apparent affinity for Na+ and GABA, and a decrease of the Na+
      concentration reduced the apparent affinity for Cl- and GABA. A comparison of
      22Na+-, 36Cl--, and 14C-labeled GABA and 14C-labeled betaine fluxes and GABA- and
      betaine-induced currents yielded a coupling ratio of Na+/Cl-/organic substrate of
      3:1:1 or 3:2:1. Based on the data, a transport model of ordered binding is
      proposed in which GABA binds first, Na+ second, and Cl- third. In conclusion,
      BGT-1 displays significant functional differences from the other members of the
      GABA transporter family.
FAU - Matskevitch, I
AU  - Matskevitch I
AD  - Department of Physiology, University of Tubingen, Tubingen 72076, Germany.
FAU - Wagner, C A
AU  - Wagner CA
FAU - Stegen, C
AU  - Stegen C
FAU - Broer, S
AU  - Broer S
FAU - Noll, B
AU  - Noll B
FAU - Risler, T
AU  - Risler T
FAU - Kwon, H M
AU  - Kwon HM
FAU - Handler, J S
AU  - Handler JS
FAU - Waldegger, S
AU  - Waldegger S
FAU - Busch, A E
AU  - Busch AE
FAU - Lang, F
AU  - Lang F
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 (Carrier Proteins)
RN  - 0 (Cations, Monovalent)
RN  - 0 (Chlorides)
RN  - 0 (GABA Plasma Membrane Transport Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 146313-33-9 (betaine plasma membrane transport proteins)
RN  - 3SCV180C9W (Betaine)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 9NEZ333N27 (Sodium)
SB  - IM
MH  - Animals
MH  - Betaine/*metabolism
MH  - Biological Transport
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cations, Monovalent/pharmacology
MH  - Chlorides/pharmacology
MH  - Dogs
MH  - Electric Conductivity
MH  - GABA Plasma Membrane Transport Proteins
MH  - Models, Biological
MH  - Oocytes
MH  - Patch-Clamp Techniques
MH  - Recombinant Proteins/metabolism
MH  - Sodium/pharmacology
MH  - Structure-Activity Relationship
MH  - Substrate Specificity
MH  - Xenopus
MH  - gamma-Aminobutyric Acid/*metabolism
EDAT- 1999/06/08 00:00
MHDA- 1999/06/08 00:01
CRDT- 1999/06/08 00:00
PHST- 1999/06/08 00:00 [pubmed]
PHST- 1999/06/08 00:01 [medline]
PHST- 1999/06/08 00:00 [entrez]
AID - 10.1074/jbc.274.24.16709 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 11;274(24):16709-16. doi: 10.1074/jbc.274.24.16709.