Inhibition of transient potassium current in cultured and acutely dissociated mouse hippocampal neurons by GABAA receptor activation.

1. The regulation of A-current, one of several transient voltage-gated potassium currents, was studied using whole cell gigaohm seal voltage-clamp techniques on hippocampal pyramidal neurons that were either acutely dissociated from postnatal mouse brain or isolated from embryonic mouse brain and grown in dissociated culture. These neurons also express gamma-aminobutyric acid-A (GABAA) receptors, the activation of which can, under some circumstances, depolarize immature neurons and the dendrites of more mature neurons. 2. Application of GABA (50 microM) reduced the amplitude of A-current when potassium current amplitude was measured during a period of slow and incomplete desensitization of IGABA. A-current was reduced to 67 +/- 9% of control (mean +/- SD, n - 14) in acutely dissociated neurons, and to 64 +/- 11% of control (n = 15) in cultured neurons. Similar A-current reductions were seen in large outside-out membrane patches pulled from somata of cultured neurons, an observation suggesting that imperfect control of membrane voltage was not responsible for A-current inhibition. 3. A-current inhibition exhibited the sensitivity expected of a GABAA-sensitive process. It was mimicked by muscimol and blocked by bicuculline, picrotoxin, and reduction of [Cl-] in the external solution. Baclophen and phaclophen, effective as agonist and antagonist on GABAB receptors, did not affect A-currents or their inhibition. Reduction in extracellular osmolarity (to increase cell swelling as might occur with Cl- entry), or removal of external HCO3- (which might flow inward through GABAA channels and cause local external acidification), did not affect A-current or its inhibition. The mechanisms of inhibition is not clear at present. 4. We suggest that reduced A-current may favor GABA-induced depolarization and consequent activation of voltage-gated calcium channels.