Functional characterization of the betaine/gamma-aminobutyric acid transporter BGT-1 expressed in Xenopus oocytes
Cited 47 times inCited 46 times in
- Functional characterization of the betaine/gamma-aminobutyric acid transporter BGT-1 expressed in Xenopus oocytes
- Matskevitch, I; Wagner, CA; Stegen, C; Broer, S; Noll, B; Risler, T; Kwon, HM; Handler, JS; Waldegger, S; Busch, AE; Lang, F
- VOLUME REGULATORY MECHANISMS; BRAIN GABA TRANSPORTER; RAT-BRAIN; MOLECULAR-CLONING; MOUSE-BRAIN; CDNA; HETEROGENEITY; CHANNELS; CELLS
- Issue Date
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- JOURNAL OF BIOLOGICAL CHEMISTRY, v.274, no.24, pp.16709 - 16716
- Betaine is an osmolyte accumulated in cells during osmotic cell shrinkage. The canine transporter mediating cellular accumulation of the osmolyte betaine and the neurotransmitter γ-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 γ- 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 = β-alanine > proline = quinidine > dimethylglycine > glycine > sarcosine. Both the V(max) and K(m) 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 K(m) 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.
- ; Go to Link
Appears in Collections:
- SLS_Journal Papers
can give you direct access to the published full text of this article. (UNISTARs only)
Show full item record
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.