ENDURING INCREASE IN MEMBRANE-ASSOCIATED PROTEIN-KINASE-C ACTIVITY IN THE HIPPOCAMPAL-KINDLED RAT

In a previous study we demonstrated that the membrane-associated protein kinase C (PKC) activity in the amygdala/pyriform cortex (AM/PC) and both the right and left hippocampus (HIPP) of rats kindled from the left HIPP increased significantly 4 weeks after the occurrence of the last seizure compared with control rats. In this study, we carried out further investigations into the enduring effect of HIPP-kindling on membrane-associated PKC activity, the protein concentrations and brain wet tissue weights of the AM/PC and right (contralateral) and left (ipsilateral) HIPP 15-16 weeks after the last generalized kindled seizure had occurred. In addition, we determined the membrane-associated PKC activity one week after the occurrence of the last partial (stage 1-3) seizure. Fifteen to sixteen weeks after the final kindled full seizure, the membrane-associated PKC activity which was expressed as mol/min per mg protein increased significantly in the AM/PC (by 62%, P < 0.02) and left HIPP (by 33%, P < 0.03) compared with control rats, whereas the cytosolic PKC activities did not differ in any brain region examined. The wet tissue weight increased significantly (by 10%, P < 0.04) in the left HIPP only. Furthermore, when it was expressed as pmol/min per mg wet tissue weight, the membrane-associated PKC activity increased significantly in the AM/PC (by 47%, P < 0.02), right HIPP (by 27%, P < 0.05) and left HIPP (by 35%, P < 0.03) compared with the controls. One week after the final partial seizure, neither the membrane-associated nor the cytosolic PKC activities in any brain region examined in the partially kindled and control groups differed significantly. These results suggest that activation of membrane-associated PKC may be involved in the long-lasting seizure susceptibility induced by kindling.