Influence of membrane potential on the sodium-dependent uptake of gamma-aminobutyric acid by presynaptic nerve terminals: experimental observations and theoretical considerations.
Sodium, potassium and veratridine were tested for their effects on the uptake of gamma-aminobutyric acid (GABA) by pinched-off presynaptic nerve terminals (synaptosomes). As noted by previous investigators, the uptake from media containing 1 mum GABA ("high-affinity" uptake) is markedly Na-dependent; the uptake averaged 65 pmoles/mg synaptosome protein x min, with [Na]0=145mm and [K]0=5mm, and declined by about 90 percent when the external Na concentration ([Na]0) was reduced to 13mm (Na replaced by Li). The relationship between [Na]0 was GABA uptake was sigmoid, suggesting that two or more Na+ ions may be required to activate the uptake of one GABA molecule. Thermodynamic considerations indicate that with a Na+/GABA stoichiometry of 2:1, the Na electrochemical gradient, alone, could provide sufficient energy to maintain a maximum steady-state GABA gradient ([GABA]i/[GABA]0) of about 104 across the plasma membrane of GABA-nergic terminals. In Ca-free media with constant [Na]0, GABA uptake was inhibited, without delay, by increasing [K]0 or by introducing 75mum veratridine; the effect of veratridine was blocked by 200 nm tetrodotoxin. The rapid onset (within 10 sec) of the veratridine and elevated-K effects implies that alterations in intra-terminal ion concentrations are not responsible for the inhibition. The uptake of GABA was inversely proportional to log [K]0. These observations are consistent with the idea that the inhibitory effects of both veratridine and elevated [K]0 may be a consequence of their depolarizing action. The data are discussed in terms of a barrier model (Hall, J.E., Mead, C.A., Szabo, G. 1973. J. Membrane Biol. 11:75) which relates carrier-mediated ionic flux to membrane potential.
D000613:Aminobutyrates / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D000613:Aminobutyrates; D013779:Tetrodotoxin; D014701:Veratridine; D012964:Sodium; D011188:Potassium