Activation of protein kinase C results in down-modulation of different recombinant GABAA-channels.

Different combinations of cloned rat brain subunits of the GABAA receptor were expressed in Xenopus oocytes. The effect of the phorbol ester PMA, an activator of protein kinase C, on the expressed GABA-gated ion current was determined. Ion currents were diminished by beta-PMA, but not by the control substance alpha-PMA, irrespective of the subunit combination studied. The mechanism of current decrease was investigated in more detail for the subunit combination alpha 5 beta 2 gamma 2. The reversal potential of the current remained unaffected, while the maximal current amplitude was decreased and the apparent Ka for GABA-dependent channel gating was shifted to higher concentrations.