Abstracts

Neuronal surface charge is a key factor determining neuronal excitability. Reduction of the negative surface charge by increasing the level of divalent cations or proton strongly shifts the activation thresholds towards more positive values. However, the physiological mechanisms regulating neuronal surface charge and associated excitability remain largely unknown. Here we studied effect of desialylation on high K/ low Mg model of epilepsy., Patch-clamp recordings of voltage-gated sodium currents were made from hippocampal slices at P3-4 rats ([italic]n[/italic]=7). Extracellular recordings of the effect of neuraminidase (NA) treatment on the probability of evoking seizures were made from CA3 pyramidal cell layer in slices from P8-21 rats using metal electrodes of 50 [micro]m diameter. For [italic]in vivo [/italic]experiments the application cannula with recording electrode was positioned into the CA3 pyramidal cell. 30[micro]l of NA-contained ACSF or NA blocker-contained ASCF were applied to the CA3 rat hippocampus, and the animal remained under anesthesia for 2 hours. Application of 10mM [K⁺][sub]o[/sub]/low [Mg²⁺][sub]o[/sub] (high K) ACSF was made by repetitive injection of 5 [micro]l-volumes., After two hours of slice incubation with NA peak of current-voltage relationship of [italic]I[sub]Na[/sub][/italic] recorded from CA3 neurons shifted toward positive potential ([sim]9mV). Application of high K⁺ ACSF induced bursting discharges and then recurrent tonic-like activity in 87% and 38% and clonic-like activity in 100% and 77% of control and NA-treated slices, respectively. Subsequently, we tested the effect of NA on the probability of evoking seizures [italic]in vivo[/italic] in rats (postnatal days 8-21). 30 [micro]l NA was applied in to the CA3 region of rat hippocampus. After two hours of incubation with NA, repetitive injection of the high K⁺ ACSF into hippocampal CA3 pyramidal layer were applied. In the control group, high K⁺ inevitably induced ictal-like discharges in all animals tested ([italic]n[/italic]=10); only two of eight rats treated with NA displayed ictal-like activity. Seizures in NA-treated rats were significantly shorter than in the control group. After incubation with a NA blocker[italic] in vivo[/italic], high K⁺ ACSF was applied to the same region of the hippocampus. In contrast with a control group of rats where seizures were triggered on the 4^th-6^th application, seizures in NA blocker treated rats appeared on the 1^st-30 ml ^rd application, and were significantly longer., Our results suggest that NA-mediated control of the level of sialic acids at the neuronal surface serves as a physiological mechanism to control the surface charge and neuronal and network excitability.[figure1],