A riluzole- and valproate-sensitive persistent sodium current contributes to the resting membrane potential and increases the excitability of sympathetic neurones

Non-adapting superior cervical ganglion (SCG) neurones with a clustering activity and sub-threshold membrane potential oscillations were occasionally recorded, suggesting the presence of a persistent sodium current (I NaP). The perforated-patch technique was used to establish its properties and physiological role. Voltage-clamp experiments demonstrated that all SCG cells have a TTX-sensitive I NaP activating at about −60 mV and with half-maximal activation at about −40 mV. The mean maximum I NaP amplitude was around −40 pA at −20 mV. Similar results were achieved when voltage steps or voltage ramps were used to construct the current–voltage relationships, and the general I NaP properties were comparable in mouse and rat SCG neurons. I NaP was inhibited by riluzole and valproate with an IC50 of 2.7 and 3.8 μM, respectively, while both drugs inhibited the transient sodium current (I NaT) with a corresponding IC50 of 34 and 150 μM. It is worth noting that 30 μM valproate inhibited the I NaP by 70% without affecting the I NaT. In current clamp, valproate (30 μM) hyperpolarised resting SCG membranes by about 2 mV and increased the injected current necessary to evoke an action potential by about 20 pA. Together, these results demonstrate for the first time that a persistent sodium current exists in the membrane of SCG sympathetic neurones which could allow them to oscillate in the sub-threshold range. This current also contributes to the resting membrane potential and increases cellular excitability, so that it is likely to play an important role in neuronal behaviour.