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.