Alternatively, one may pharmacologically suppress or enhance, respectively, intrinsic plasticity processes depending on whether they reflect commencing epileptogenesis and are related to the occurrence of spontaneous seizures or whether they represent a WY 14643 PPAR inhibitor protection or repair program . Thus, blocking Cav3.2 channels at an early stage in order to prevent the development of burst firing and Ca2+ overload in neurons has been envisaged as one option. However, the T-type Ca2+ channel blocker ethosuximide turned out to be inactive or not preventing epileptogenesis in animal models . Assuming that indications of a strengthening of b-AP attenuation reflect a program that protects CA1 pyramidal cell dendrites from Ca2+ overload, any pharmacological intervention which further strengthens b-AP attenuation would be desirable. As our b-AP imaging data suggest, this may be accomplished with the Kv4 current activator NS5806 in CA1 pyramidal cells of the juvenile murine hippocampus. The effects of NS5806 on excitability, AP properties and b-AP-induced Ca2+ signal dynamics were in part similar to the ones seen after acute SE . On the other hand, the effects of NS5806 on AP frequency, AP amplitude and ADP integral were opposite to the ones seen after acute SE, and, also unlike acute SE, NS5806 left the AP threshold unaffected. Obviously, during acute SE certain remodeling processes may take place which are not mimicked by NS5806. On the other hand, the action of NS5806 is known to be not restricted to Kv4 channels . Finally, it should also be noted that Kv4 channels do not only mediate ISA but also a transient outward current in cardiac myocytes and that, at least in the dog heart, the NS5806-mediated potentiation of Ito has been found to recapitulate certain features of Brugada syndrome, a form of cardiac BMS-354825 arrhythmia . Thus, NS5806, which we used in an attempt to simulate the results of the present study, is certainly not a good AED candidate. However, compounds related to NS5806 but with a more specific action on Kv4.2 rather than Kv4.3, to be discovered or developed in the future, may become useful AEDs. In summary, our data provide evidence for intrinsic plasticity mechanisms in CA1 pyramidal cells already active during acute SE. In this time interval detrimental remodeling processes, which reflect the onset of epileptogenesis, may coexist with remodeling processes belonging to a protection or repair program of the brain. Signs of acute alterations of AP dynamics may be related to either of the two scenarios, and appropriate assignment must be made in order to decide whether to suppress or maybe even enhance the observed plasiticity processes. Strengthening of b-AP attenuation may be related to a program that protects dendritic structures from excitotoxicity.