THE INCREASE IN CL- PERMEATION ACROSS THE DEITERS NEURON MEMBRANE BY GABA ON ITS CYTOPLASMIC SIDE IS ABOLISHED BY PROTEIN-KINASE-C (PKC) ACTIVATORS

1. Cl- ion outward permeation across microdissected Deiters' neuron pl asma membranes is augmented by GABA on the membrane cytoplasmic side. When these neurons are preincubated with a PKC activator, phorbol-12,1 3-dibutyrate (PdBu), there is a complex pattern of effects on basal an d GABA-activated Cl-36(-) in --> out permeation. A distinct fact is an increase in basal Cl- passage and a disappearance of the 10(-6) M GAB A effect at [PdBu] = 0.1 mu M. 2. Likewise, 0.1 mu M oleylacetylglycer ol (OAG) treatment erases the effect completely, further supporting a role for PKC in modulating GABA-stimulated Cl- in --> out permeation. 3. The inactive ester, phorbol-12,13-didecanoate (Pdd), at 0.1 mu M, d oes not affect GABA stimulation of Cl- passage. 4. High concentrations (15-20 mu M) of OAG and PdBu block the ''intracellular'' GABA effect. However, the 20 mu M PdBu effect is reversed by 30 mu M H7. 5. These results indicate a role of endogenous PKC in Cl- extrusion by GABA(A) receptors on the cytoplasmic side of the Deiters' neuron membrane.