GABA-induced potassium channels in cultured neurons

Abstract

When $\gamma $-aminobutyric acid (GABA) or baclofen were applied to cultured rat hippocampal neurons, single-channel potassium currents appeared after a delay of 30 s or more in patches of membrane on the cell surface isolated from the agonists by the recording pipette. The appearance of currents in patches not exposed to agonist, the delay in their appearance and the suppression of currents in cells pre-incubated with pertussis toxin indicate the involvement of an intracellular second messenger system. The channels were associated with a GABA$_{\text{B}}$ receptor rather than a GABA$_{\text{A}}$ receptor as they were blocked by saclofen, a GABA$_{\text{B}}$ antagonist, but were not affected by bicuculline, a GABA$_{\text{A}}$ antagonist. A feature of the single channel currents was their variable amplitude: they had a maximum conductance of ca. 70 pS and displayed many lower conductance states that were integral multiples of 5-6 pS. In several cells exposed to GABA or baclofen, first small currents and then progressively larger currents appeared: current amplitude was a multiple of an elementary current. It is suggested that binding of GABA to GABA$_{\text{B}}$ receptors activates a second messenger system causing opening of oligomeric potassium channels.