Inhibitors of the γ-aminobutyric acid transporter 1 (GAT1) do not reveal a channel mode of conduction |
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Authors: | Edward Matthews Jr Ali Rahnama-Vaghef Sepehr Eskandari |
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Institution: | aBiological Sciences Department, California State Polytechnic University, 3801 West Temple Avenue, Pomona, CA 91768-4032, USA |
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Abstract: | We expressed the γ-aminobutyric acid (GABA) transporter GAT1 (SLC6A1) in Xenopus laevis oocytes and performed GABA uptake experiments under voltage clamp at different membrane potentials as well as in the presence of the specific GAT1 inhibitors SKF-89976A and NO-711. In the absence of the inhibitors, GAT1 mediated the inward translocation of 2 net positive charges across the plasma membrane for every GABA molecule transported into the cell. This 2:1 charge flux/GABA flux ratio was the same over a wide range of membrane potentials from −110 mV to +10 mV. Moreover, when GABA-evoked (500 μM) currents were measured at −50 and −90 mV, neither SKF-89976A (5 and 25 μM) nor NO-711 (2 μM) altered the 2:1 charge flux/GABA flux ratio. The results are not consistent with previous hypotheses that (i) GABA evokes an uncoupled channel-mediated current in GAT1, and (ii) GAT1 inhibitors block the putative uncoupled current gated by GABA. Rather, the results suggest tight coupling of GAT1-mediated charge flux and GABA flux. |
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Keywords: | Neurotransmitter:sodium symporter SLC6 Sodium- and chloride-coupled transport Neurotransmitter transporter GABA Human GAT1 SLC6A1 Channel mode Uptake under voltage clamp |
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