INHIBITION OF TRANSIENT POTASSIUM CURRENT IN CULTURED AND ACUTELY DISSOCIATED MOUSE HIPPOCAMPAL-NEURONS BY GABA(A) 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 ac utely dissociated from postnatal mouse brain or isolated from embryoni c mouse brain and grown in dissociated culture. These neurons also exp ress gamma-aminobutyric acid-A (GABAA) receptors, the activation of wh ich can, under some circumstances, depolarize immature neurons and the dendrites of more mature neurons. 2. Application of GABA (50 mu M) re duced the amplitude of A-current when potassium current amplitude was measured during a period of slow and incomplete desensitization of I-G ABA. A-current was reduced to 67 +/- 9% of control (mean +/- SD, n = 1 4) in acutely dissociated neurons, and to 64 +/- 11% of control (n = 1 5) in cultured neurons. Similar A-current reductions were seen in larg e 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 wa s mimicked by muscimol and blocked by bicuculline, picrotoxin, and red uction of [Cl-] in the external solution. Baclophen and phaclophen, ef fective as agonist and antagonist on GABA, 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 o f external HCO; (which might flow inward through GABAA channels and ca use local external acidification), did not affect A-current or its inh ibition. The mechanisms of inhibition is not clear at present. 4. We s uggest that reduced A-current may favor GABA-induced depolarization an d consequent activation of voltage-gated calcium channels.