GABA and bicuculline actions on mouse spinal cord and cortical neurons in cell culture

The neutral amino acid gamma-aminobutyric acid (GABA) produced membrane hyperpolarization and increased membrane chloride ion conductance of spinal cord (SC) and cortical (CTX) neurons in cell culture. GABA dose-response curves were obtained for SC neurons by pressure applying known concentrations of GABA from micropipettes with large tips (miniperfusion pipettes). GABA response threshold was about 2 micrometers and large responses were elicited at GABA concentrations greater than 10 micrometers. Bicuculline (BICUC) (0.1-10 micrometers) reversibly antagonized GABA responses on both SC and CTX neurons with a half maximal inhibitory concentration of about 1 micrometer. BICUC antagonism of GABA responses was competitive (Lineweaver-Burke analysis). These results are compared with data on GABA and BICUC displacement of [3H]GABA binding to membranes of SC and CTX neurons in cell culture. It is suggested that high affinity GABA receptors are likely to be relevant for postsynaptic GABA responses while low affinity GABA receptors may be presynaptic.