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

Isaev D, Ivanchick G, Khmyz V, Isaeva E, Savrasova A, Krishtal O, Holmes GL, Maximyuk O. Surface charge impact in low-magnesium model of seizure in rat hippocampus. J Neurophysiol 107: 417-423, 2012. First published October 26, 2011; doi:10.1152/jn.00574.2011.-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+](o) to 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+](o) to 1 mM is identical to the increase in [K+](o) to 5 mM in terms of changes in cellular excitability and seizure threshold. An increase of [Ca2+](o) to 3 mM completely abolished SLA generation even in the presence of 5 mM [K+](o). A large variation in the ability of [Ca2+](o) to 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.