Properties of gamma-aminobutyric acid (GABA) receptor binding in rat brain synaptic membrane fractions.

The binding of GABA to crude synaptic membrane fractions of the rat central nervous system in the absence of sodium appears to involve synaptic receptor sites for GABA. The sodium-independent GABA receptor binding differs in a number of features from sodium-dependent GABA binding. In fresh tissue sodium-dependent GABA binding is about 10 times greater than sodium-independent binding, while freezing and thawing the brain membranes virtually abolishes sodium-dependent binding but increases sodium-independent GABA receptor binding about 2-fold. Both sodium-dependent and -independent GABA binding are saturable processes with dissociation constants of 1.2 muM and 0.37 muM respectively. Sodium-dependent GABA binding is much more sensitive to extremes of temperature and pH than is sodium-dependent GABA binding. In addition, regional variations in synaptosomal uptake of GABA, sodium-dependent and sodium-independent GABA binding are markedly different. Also, amino acids and drugs differ in their potencies as inhibitors of sodium-dependent and sodium-independent GABA binding, with the relative affinity of several agents for sodium-independent GABA receptor sites closely paralleling their abilities to mimic neurophysiologic effects of GABA at postsynaptic receptors. Though there are some similarities between the influence of drugs and amino acid analogues on sodium-dependent binding and synaptosomal accumulation of GABA there are also marked differences such as a much greater affinity of beta-alanine for the sodium-dependent GABA binding sites than for synaptosomal GABA uptake. This suggests that the sodium-dependent GABA binding may involve uptake sites for the GABA accumulating system of glia rather than for neuronal GABA transport.