Voltage-gated sodium (NaV) channel blockade by plant cannabinoids does not confer anticonvulsant effects per se

Cannabidiol (CBD) is a non-psychoactive, well-tolerated, anticonvulsant plant cannabinoid, although its mechanism(s) of seizure suppression remains unknown. Here, we investigate the effect of CBD and the structurally similar cannabinoid, cannabigerol (CBG), on voltage-gated Na+ (NaV) channels, a common anti-epileptic drug target. CBG’s anticonvulsant potential was also assessed in vivo. CBD effects on NaV channels were investigated using patch-clamp recordings from rat CA1 hippocampal neurons in brain slices, human SH-SY5Y (neuroblastoma) cells and mouse cortical neurons in culture. CBG effects were also assessed in SH-SY5Y cells and mouse cortical neurons. CBD and CBG effects on veratridine-stimulated human recombinant NaV1.1, 1.2 or 1.5 channels were assessed using a membrane potential-sensitive fluorescent dye high-throughput assay. The effect of CBG on pentyleneterazole-induced (PTZ) seizures was assessed in rat. CBD (10M) blocked NaV currents in SH-SY5Y cells, mouse cortical neurons and recombinant cell lines, and affected spike parameters in rat CA1 neurons; CBD also significantly decreased membrane resistance. CBG blocked NaV to a similar degree to CBD in both SH-SY5Y and mouse recordings, but had no effect (50-200mg/kg) on PTZ-induced seizures in rat. CBD and CBG are NaV channel blockers at micromolar concentrations in human and murine neurons and recombinant cells. In contrast to previous reports investigating CBD, CBG had no effect upon PTZ-induced seizures in rat, indicating that NaV blockade per se does not correlate with anticonvulsant effects.

The impact of location and type on the performance of Low-Voltage network connected Battery Energy Storage Systems

This paper assesses the impact of the location and configuration of Battery Energy Storage Systems (BESS) on Low-Voltage (LV) feeders. BESS are now being deployed on LV networks by Distribution Network Operators (DNOs) as an alternative to conventional reinforcement (e.g. upgrading cables and transformers) in response to increased electricity demand from new technologies such as electric vehicles. By storing energy during periods of low demand and then releasing that energy at times of high demand, the peak demand of a given LV substation on the grid can be reduced therefore mitigating or at least delaying the need for replacement and upgrade. However, existing research into this application of BESS tends to evaluate the aggregated impact of such systems at the substation level and does not systematically consider the impact of the location and configuration of BESS on the voltage profiles, losses and utilisation within a given feeder. In this paper, four configurations of BESS are considered: single-phase, unlinked three-phase, linked three-phase without storage for phase-balancing only, and linked three-phase with storage. These four configurations are then assessed based on models of two real LV networks. In each case, the impact of the BESS is systematically evaluated at every node in the LV network using Matlab linked with OpenDSS. The location and configuration of a BESS is shown to be critical when seeking the best overall network impact or when considering specific impacts on voltage, losses, or utilisation separately. Furthermore, the paper also demonstrates that phase-balancing without energy storage can provide much of the gains on unbalanced networks compared to systems with energy storage.