LONG-LASTING CHANGE IN THE MEMBRANE-ASSOCIATED PROTEIN-KINASE-C ACTIVITY IN THE HIPPOCAMPAL KINDLED RAT

The effect of hippocampal kindling on protein kinase C (PKC) activity and protein concentration was investigated in rat amygdala/pyriform cortex (AM/PC) and right (contralateral) and left (ipsilateral) hippocampus (HIPP). There was no difference in cytosolic PKC activity between control and kindled groups in any part of the brain. The membrane-associated PKC activity was altered as follows. One week after the last seizure, it was significantly increased in both right (by 26%, P < 0.05) and left HIPP (by 30%, P < 0.02). Four weeks after the last seizure, it was significantly increased in the AM/PC (by 14%, P < 0.02), right HIPP (by 37%, P < 0.01) and left HIPP (by 24%, P < 0.05). The protein concentrations in the crude cytosolic extracts prior to elution of PKC through DE-52 columns were significantly increased in the AM/PC (by 11%, P < 0.05) and right HIPP (by 18%, P < 0.02) 4 weeks after the last seizure. In the membrane extracts, there was a significant increase by 23% (P < 0.02) in the left HIPP 1 week after the last seizure. In the fraction co-eluted with PKC, a significant increase in protein concentration of the cytosolic preparation was confirmed in the AM/PC (by 12%, P < 0.05) as well as in the left HIPP (by 15%, P < 0.05) 4 and 1 weeks respectively after the last seizure. In the membrane preparation, there were significant increases in the right HIPP (by 26%, P < 0.01) and left HIPP (by 21%, P < 0.05) 1 week after the last seizure and in the right HIPP (by 42%, P < 0.01) 4 weeks after the last seizure. However, the ratio of protein concentration to wet tissue weight did not differ significantly between control and kindled groups in any brain area examined. These results suggest that activation of PKC may play an important role in the kindling mechanism.