Downregulation of ISA-mediating Kv4.2 channels was made responsible for this chronic form of b-AP modulation , and in support of this notion, the authors found a decrease in total Kv4.2 protein and an increase in the fraction of extracellular receptor kinase -phosphorylated Kv4.2 protein . Kv4.2 downregulation in the chronic disease state of this model was also supported by immunocytochemistry experiments . Weakened b-AP attenuation in the dendrite due to a chronic SE-related downregulation of Kv4.2 channels represents an acquired channelopathy . To assess the causal relationship between altered b-AP dynamics and epileptogenesis it is important to determine the time of onset of changes in b-AP dynamics. In a first attempt to answer this question, we performed b-AP imaging experiments on individual CA1 pyramidal cells immediately after a 1�C2 h period of kainate-induced SE in mice. Although the measurements performed in the present study are inKU-0059436 direct , our results suggest a strengthening of b-AP attenuation between 5 and 200 mm from the soma, a range where no difference between SE and control had been seen previously in the chronic phase of the rat pilocarpine model . It should be noted that the range of measurement in our study was smaller than in the study by Bernard and coworkers , and we have no information about b-AP dynamics beyond 200 mm from the soma, the dendritic region, where drastic differences had been seen in the chronic pilocarpine model both with respect to b-AP suppression and with respect to EPSP generation mediated by direct input from the entorhinal cortex . In our experiments the suppression of the b-AP-induced Ca2+ signal was almost complete at the largest distance measured, and an increase in amplitude beyond a distance of 200 mm from the soma seems unlikely. Assuming that both before and during epileptogenesis ISA governs b-AP dynamics, our b-AP imaging results may be explained by an augmentation of ISA. There is experimental evidence of acute and subacute SE-related Kv4.2 channel remodeling, however, the data reported in the literature are diverse: Su and coworkers have tested protein expression levels in the rat pilocarpine model. They found that Kv4.2 protein and Kv channel TH-302 interacting protein 1, a bsubunit of Kv4.2, were transiently upregulated in a seizuredependent manner between 3 and 24 h after SE induction. These authors also measured 4-AP-induced Ca2+ elevations in CA1 pyramidal cells and reported a 2-fold larger rise in the SE group compared to control 24 h after pilocarpine injection. This finding was interpreted as an SE-related upregulation of functional Kv4.2 channels to be targeted by 4-AP .