Asymmetric diffusion into the postsynaptic neuron: an extremely efficient mechanism for removing excess GABA from synaptic clefts on the Deiters' neurone plasma membrane

Abstract

Microdissected Deiters' neuron plasma membranes have been used for studying the passage of GABA through the membrane both in the inward and outward direction. Working with 0.2 mM GABA in the compartment simulating the outside of the neurone and with 2.0 mM GABA in the one simulating the inside we found a net transport of GABA towards the inside. This mechanism does not require a Na+ ion gradient across the membrane. The nature of the transport process involved was studied by determining the rate of [3H]-GABA inward passage as a function of GABA concentration (1 nM - 800 microM) on the outward side of the membrane. The results have shown that until 50 microM a diffusion process (v = D1 X C, where D1 = 3.1 X 10(-11) 1/micron 2 X sec) is the sole mechanism involved. Above 50 microM a second diffusion process is activated v = D2 X (C - 50 X 10(-6), where D2 = 2.8 X 10(-11) 1/micron 2 X sec. Taking in account both inward and outward directed diffusion, one can calculate 16 microM as the equilibrium concentration of GABA on the outward side of the membrane. From a kinetic point of view, these diffusion processes are able to reduce GABA concentration in a synaptic cleft from 3 mM to 20 microM within 3 mu sec. These diffusion systems are discussed as extremely efficient in removing the excess of released GABA in the synaptic cleft.