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- Title
A riluzole- and valproate-sensitive persistent sodium current contributes to the resting membrane potential and increases the excitability of sympathetic neurones.
- Authors
Lamas, J. Antonio; Romero, Marcos; Reboreda, Antonio; Sánchez, Estela; Ribeiro, Sandro J.
- Abstract
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 ( INaP). 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 INaP activating at about −60 mV and with half-maximal activation at about −40 mV. The mean maximum INaP 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 INaP properties were comparable in mouse and rat SCG neurons. INaP 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 ( INaT) with a corresponding IC50 of 34 and 150 μM. It is worth noting that 30 μM valproate inhibited the INaP by 70% without affecting the INaT. 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.
- Subjects
SODIUM; EXCITATION (Physiology); SYMPATHETIC nervous system; NEURONS; GENE expression; VOLTAGE-clamp techniques (Electrophysiology); VALPROIC acid
- Publication
Pflügers Archiv: European Journal of Physiology, 2009, Vol 458, Issue 3, p589
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-009-0648-0