Surface charge impact in low-magnesium model of seizure in rat hippocampus

Abstract

Putative mechanisms of induction and maintenance of seizure-like activity (SLA) in the low Mg2+model of seizures are: facilitation of NMDA receptors and decreased surface charge screening near voltage-gated channels. We have estimated the role of such screening in the early stages of SLA development at both physiological and room temperatures. External Ca2+and Mg2+promote a depolarization shift of the sodium channel voltage sensitivity; when examined in hippocampal pyramidal neurons, the effect of Ca2+was 1.4 times stronger than of Mg2+. Removing Mg2+from the extracellular solution containing 2 mM Ca2+induced recurrent SLA in hippocampal CA1 pyramidal layer in 67% of slices. Reduction of [Ca2+]oto 1 mM resulted in 100% appearance of recurrent SLA or continuous SLA. Both delay before seizure activity and the inter-SLA time were significantly reduced. Characteristics of seizures evoked in low Mg2+/1 mM Ca2+/3.5 K+were similar to those obtained in low Mg2+/2 Ca2+/5mM K+, suggesting that reduction of [Ca2+]oto 1 mM is identical to the increase in [K+]oto 5 mM in terms of changes in cellular excitability and seizure threshold. An increase of [Ca2+]oto 3 mM completely abolished SLA generation even in the presence of 5 mM [K+]o. A large variation in the ability of [Ca2+]oto stop epileptic discharges in initial stage of SLA was found. Our results indicate that surface charge of the neuronal membrane plays a crucial role in the initiation of low Mg2+-induced seizures. Furthermore, our study suggests that Ca2+and Mg2+, through screening of surface charge, have important anti-seizure and antiepileptic properties.