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

Abstract

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 INa. It shifted the INa 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 INa altered the electrical activity of neurons in vivo and OD-1 could potentially serve as a novel seizure and excitotoxicity model.

The Integrated Effects of Brivaracetam, a Selective Analog of Levetiracetam, on Ionic Currents and Neuronal Excitability

“…In both of the OD-1 and lithium-pilocarpine groups, the seizure characteristics of the rats during acute seizures were similar to those reported elsewhere [ 51 , 55 , 56 ]. The seizures were scored using the Racine scale [ 56 ].…”

“…In a final series of studies, we evaluated the effects of BRV versus LEV on acute seizures in different animal models, including a sodium channel agonism-based OD-1 model [ 55 ] and the well-established lithium-pilocarpine-induced epilepsy model. We have recent characterized OD-1, a scorpion toxin, which could produce a concentration-, time-, and state-dependent rise in the peak amplitude of I Na , shifting the I Na inactivation curve to a less negative potential and increasing the frequency of spontaneous action currents.…”

“…We have recent characterized OD-1, a scorpion toxin, which could produce a concentration-, time-, and state-dependent rise in the peak amplitude of I Na , shifting the I Na inactivation curve to a less negative potential and increasing the frequency of spontaneous action currents. It could generate a significantly higher frequency of spontaneous seizures and epileptiform discharges compared with lithium-pilocarpine- or kainic acid-induced epilepsy, with comparable pathological changes [ 55 ]. We found in the OD-1 model that BRV had significant effects on the sustained time of severe seizures (stage 4 and above, seconds) (NS: 450 ± 25, LEV: 390 ± 22, BRV: 220 ± 20) ( p < 0.05) compared to the control group ( Figure 10 A).…”

“…The seizures were scored using the Racine scale [ 56 ]. The rats were given zoletil (50 mg/kg, ip), xylazine (20 mg, ip), and atropine (0.2 mg/kg, sc) to diminish the seizures if their status epilepticus lasted for 20 min [ 51 , 55 , 56 , 57 , 58 ]. Mortality was calculated during the first 24 h after seizure onset.…”

Editorial to the Special Issue “Electrophysiology”

“…An intrahippocampal injection of OD-1 was observed to generate a higher frequency of spontaneous seizures and epileptiform discharge in lithium–pilocarpine- or kainic acid-induced epilepsy. The OD-1-induced modifications of I Na could thus serve as a novel seizure and excitotoxicity model [ 7 ].…”