Cross-modulation of glycine-activated Cl- channels by protein kinase C and cAMP-dependent protein kinase in the rat.

1. The cross-modulation of glycine responses by cyclic-AMP-dependent protein kinase (PKA) and protein kinase C (PKC) was determined in acutely dissociated trigeminal neurons. 2. Whole-cell glycine-evoked Cl- current (IGly) was recorded using the patch clamp technique. Protein kinases and their inhibitors were intracellularly perfused into the cells. 3. Both PKA and PKC when applied separately potentiated IGly. 4. When PKA and PKC were sequentially applied, PKC could not increase the IGly any further after the glycine responses were enhanced by PKA. 5. In 42% of our cells, IGly increased spontaneously. Endogenous PKA was found to mediate the increase. PKC had no effects on IGly in these cells. 6. The effect of PKA on IGly was studied in PKC-pretreated cells. PKA failed to potentiate IGly in these cells, suggesting that the PKA action also depends on the activity of PKC inside the cells. 7. These results suggest that the PKC action on IGly is conditional upon the modulation of the currents by PKA and vice versa. This cross-regulation of ligand-gated channel activity by protein kinases may play a role in neuronal integration and synaptic plasticity.