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 (I-Gly) 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 I-Gly. 4. When PKA and PKC were sequentially applied, PKC could not increase the I-Gly any further after the glycine responses were enhanced by PKA. 5. In 42% of our cells, I-Gly increased spontaneously. Endogenous PKA was found to mediate the increase. PKC had no effects on I-Gly in these cells. 6. The effect of PKA on I-Gly was studied in PKC-pretreated cells. PKA failed to potentiate I-Gly 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 I-Gly 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.