Corticotropin Releasing Factor Mediates KCa3.1 Inhibition, Hyperexcitability, and Seizures in Acquired Epilepsy

Temporal lobe epilepsy (TLE), the most common focal seizure disorder in adults, can be instigated in experimental animals by convulsant-induced status epilepticus (SE). Principal hippocampal neurons from SE-experienced epileptic male rats (post-SE neurons) display markedly augmented spike output compared with neurons from nonepileptic animals (non-SE neurons). This enhanced firing results from a cAMP-dependent protein kinase A-mediated inhibition of K Ca 3.1, a subclass of Ca 21gated K 1 channels generating the slow afterhyperpolarizing Ca 21 -gated K 1 current (I sAHP ). The inhibition of K Ca 3.1 in post-SE neurons leads to a marked reduction in amplitude of the I sAHP that evolves during repetitive firing, as well as in amplitude of the associated Ca 21 -dependent component of the slow afterhyperpolarization potential (K Ca -sAHP).