| Background:Temporal lobe epilepsy is one of the main types of the intractable epilepsy in adults.It is an challenge for clinic reseachers to prevent and treat it more effectively.Ion channel may plays an important role in the etiology and pathogensis of epilepsy,especially in intractable epilepsy.The relationship between potassium channel and epilepsy has been conformed in some types of epileptic syndroms. Inwardly rectifying potassium channel(Kir) is one of the potassium channels which can maintain the resting membrane potential and modify neuronal excitability. Epilepsy may relate to the abnormality of Kir channels' function or expression.Kir channel family has many subtypes,one of which is Kir2.3 channel.It both expresses in the cortex and hippocampus,and it has been found that the expression of Kir2.3 mRNA and protein was significantly decreased in the hippocampus of chronic temporal lobe epileptic patients.Therefore,Kir2.3 channel may be an important molecular foundation of epilepsy.Purpose:To set up an chronic temporal lobe epileptic rat model,observe the changes of Kir2.3 mRNA and protein in different time points in the hippocampus of the model and discuss the relationship between Kir2.3 channel and the pathogenesis of chronic temporal lobe epilepsy;to investigate the effect of tenidap,an special opener of Kir2.3 channel,to the behaviors of epileptic rats,expression of Kir2.3mRNA and protein, and discuss the probablility of potassium channel agonist as an antiepileptic drug. Materials and Methods:We used pilocarpine-induced chronic temporal lobe epileptic rat model.Rats were randomly divided into normal control group and 0,6,72 hour(s)and 2 weeks after status epilepticus(SE) groups,respectively.Each group has six rats.The expression of Kir2.3 mRNA and protein was measured by reverse transcription polymerase chain reaction(RT-PCR) and Western Blot.Tenidap was given to the rats by intraperitoneal injection,and we observed wether it would do something to the behavior of rats and the expression of Kir2.3mRNA and protein in hippocampus.Results:1.After the injection of pilocarpine,it took about 48 minutes averagely for all rats to induce SE.The rate of successful SE model was 94.6%and mortality was 6.6%. All the surviving SE rats were induced chronic temporal lobe epilepsy between 5 days and 2 weeks after SE.The rate of successful chronic model was 93.4%.The ratioes of Kir2.3 mRNA andβ-actin in normal control rats and in the rats 0,6,72 hour(s),2 weeks after SE were 0.080±0.030,0.103±0.045,0.164±0.026,0.132±0.024, 0.011±0.008,respectively.The ratio significantly increased in the rats 6 hours after SE than normal control group.At the time point 72 hours after SE,the expression of Kir2.3 mRNA was still higher,but it already decreased than the 6 hours'group.When detected 2 weeks after SE,we found the ratio significantly decreases than normal control.The ratioes of Kir2.3 protein and GAPDH in propotional time points were 0.305±0.030,0.263±0.028,0.767±0.167,0.498±0.077,0.176±0.026, respectively.The changing tendency of protein consistented with the mRNA. 2.After the injection of tenidap,it took about 54 minutes averagely for all rats to induce SE and the rats were less irritating than the group without tenidap.The ratioes of Kir2.3 mRNA andβ-actin in normal control rats and in the rats without or with tenidap were 0.080±0.030,0.011±0.008,0.021±0.006,respectively.The ratioes of Kir2.3 protein and GAPDH in propotional groups were 0.305±0.030,0.176±0.026, 0.636±0.140.We found tenidap could significantly increase the expression of Kir2.3 mRNA and protein at 2 weeks after SE.Conclusions:1.The chronic temporal lobe epileptic rat model was successful and it could be used for the reseach.The change of Kir2.3 channel may be a chronic dynamic process.The changes of its mRNA and protein in acute period may be a stress reaction or an self-protection.Two weeks after SE,just when the rats had spontaneous recurrent seizures,may be a reversal point in the changes of Kir2.3 expression,and then becomes one of the base of epileptogenesis.2.Tenidap could increase the expression of Kir2.3 mRNA and protein in chronic temporal lobe epileptic rats.These changes may do some reparation to the inwardly rectification, buffer the extracellular potassium load,maintain the resting membrane potential and decrease the charges finally.Our reseach could provide some evidence for the potassium channel agonists to become one of the antiepileptic drugs in future. |
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