The Specific Effects of OD-1, a Peptide Activator, on Voltage-Gated Sodium Current and Seizure Susceptibility.

OD-1, a scorpion toxin, has been previously recognized as an activator of voltage-gated Na currents. To what extent this agent can alter hippocampal neuronal Na currents and network excitability and how it can be applied to neuronal hyperexcitability research remains unclear. With the aid of patch-clamp technology, it was revealed that, in mHippoE-14 hippocampal neurons, OD-1 produced a concentration-, time-, and state-dependent rise in the peak amplitude of . It shifted the inactivation curve to a less negative potential and increased the frequency of spontaneous action currents. Further characterization of neuronal excitability revealed higher excitability in the hippocampal slices treated with OD-1 as compared with the control slices. A stereotaxic intrahippocampal injection of OD-1 generated a significantly higher frequency of spontaneous seizures and epileptiform discharges compared with intraperitoneal injection of lithium-pilocarpine- or kainic acid-induced epilepsy, with comparable pathological changes. Carbamazepine significantly attenuated OD-1 induced seizures and epileptiform discharges. The OD-1-mediated modifications of altered the electrical activity of neurons in vivo and OD-1 could potentially serve as a novel seizure and excitotoxicity model.