Electrophysiological properties of two axonal sodium channels, Na v 1.2 and Na v 1.6, expressed in mouse spinal sensory neurones

Sodium channels Na v 1.2 and Na v 1.6 are both normally expressed along premyelinated and myelinated axons at different stages of maturation and are also expressed in a subset of demyelinated axons, where coexpression of Na v 1.6 together with the Na + /Ca 2+ exchanger is associated with axonal injury. It has been difficult to distinguish the currents produced by Na v 1.2 and Na v 1.6 in native neurones, and previous studies have not compared these channels within neuronal expression systems. In this study, we have characterized and directly compared Na v 1.2 and Na v 1.6 in a mammalian neuronal cell background and demonstrate differences in their properties that may affect neuronal behaviour. The Na v 1.2 channel displays more depolarized activation and availability properties that may permit conduction of action potentials, even with depolarization. However, Na v 1.2 channels show a greater accumulation of inactivation at higher frequencies of stimulation (20–100 Hz) than Na v 1.6 and thus are likely to generate lower frequencies of firing. Na v 1.6 channels produce a larger persistent current that may play a role in triggering reverse Na + /Ca 2+ exchange, which can injure demyelinated axons where Na v 1.6 and the Na + /Ca 2+ exchanger are colocalized, while selective expression of Na v 1.2 may support action potential electrogenesis, at least at lower frequencies, while producing a smaller persistent current.