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Background: Na+/Ca2+ exchanger (NCX) plays a crucial role in pentylenetetrazol-induced convulsion.However, it is unclear whether NCX is critically involved in hyperthermia-induced convulsion.In this study, we examined the potential changes in NCX3 in the hippocampus and cerebrocortex of rats with hyperthermia-induced convulsion.Methods: Twenty-one Sprague Dawley rats were randomly assigned to control group, convulsion-prone group and convulsion-resistant group (n =7 in each group).Whole-cell patch-clamp method was used to record NCX currents.Both the West blotting analysis and immunofluorescence labeling techniques were used to examine the expression of NCX3.Results: NCX currents were decreased in rats after febrile convulsion.Compared to the control group, NCX3 expression was decreased by about 40% and 50% in the hippocampus and cerebrocortex of convulsion-prone rats, respectively.Furthermore, the extent of reduction in NCX3 expression seemed to correlate with the number of seizures.Conclusions: There is a significant reduction in NCX3 expression in rats with febrile convulsions.Our findings also indicate a potential link between NCX3 expression, febrile convulsion in early childhood, and adult onset of epilepsy.