Abstracts

Following status epilepticus (SE), hippocampal neurons exhibit dramatic changes in their intrinsic membrane properties and firing mode. However, little is know about molecular mechanisms underlying this intrinsic neuronal plasticity. Here, we have analyzed altered transcription of members of two families of voltage-dependent ion channels (all voltage-dependent Ca²⁺ channel subunits and the K⁺ channel subunits giving rise to transient A-type channels K[sub]v1.4 [/sub], K[sub]v3.3 [/sub], K[sub]v3.4 [/sub], K[sub]v4.2 [/sub] and K[sub]v4.3 [/sub]) following pilocarpine-induced SE.
mRNA was isolated either from hippocampal CA1 microslices or from laser-dissected individual CA1 neurons. Using synaptophysin as reference gene, quantitative real-time RT-PCR was applied for mRNA alternations of the voltage-dependent ion channels.
It revealed transiently increased expression of the T-type Ca²⁺ channel subunit Ca[sub]v3.2[/sub] on day 3 after pilocarpine-induced SE (4-fold increase). The expression of accessory Ca²⁺ channel subunits ([beta][sub]1[/sub],[beta][sub]3[/sub] and [alpha][sub]2[/sub][delta]) was also transiently increased at day 3 following SE. Amongst the K⁺ channel subunits, the mRNAs encoding K[sub]v4.2[/sub] (34.3% decrease) and K[sub]v1.4[/sub] (24.4% decrease), were significantly decreased at day 30 after pilocarpine injection.
In conclusion, up-regulation of subthreshold operated T-type Ca²⁺ channels in concert with down-regulation of transient A-type K⁺ channels may contribute to the marked increase in intrinsic excitability seen in CA1 neurons following SE.
[Supported by: DFG (SFB TR3), BMBF (NGFN TP11, 15) and BONFOR]