Activation of endogenous protein kinase C enhances currents through alpha 1 and alpha 2 glycine receptor channels.

The effects of Ca2+ /phospholipid dependent (PKC) phosphorylation on the current amplitudes of alpha 1 and alpha 2 glycine receptors expressed in Xenopus oocytes were examined by whole cell voltage clamp recording. In studies using phorbol esters, PKC phosphorylation has been shown to reduce glycine-induced currents. Endogenous PKC activation by pretreatment with serum, however, enhanced the currents to around 140% in both alpha 1 and alpha 2 glycine receptors. This effect was completely blocked by a specific PKC inhibitor, GF109203X. Instead, treatment with a potent PKC activator, 12-O-tetradecanoylphorbol-13-acetate (TPA) revealed a decrease in glycine-gated channel currents. Thus, the present results demonstrate that glycine receptor phosphorylation mediated by endogenous pathway of PKC activation potentiates glycine-induced currents and phorbol esters may have a direct action on glycine receptor channels independent of PKC activation.