Persistent Na-channels: Origin and function

Voltage-dependent sodium channels have a decisive role in the generation of action potentials (AP) in many types of cells. In addition to the fast inactivating Na-current, associated with AP generation, the Na-channel can give rise to a noninactivating or persistent Na-current. The latter current generally comprises up to 5% of the transient current having important physiological consequences. It was established that persistent Na-currents have functional significance in setting the membrane potential in a subthreshold range regulating by this way dendritic depolarisations, repetitive firing and enhancing synaptic transmission. Voltage dependent sodium channel genes have been identified in a variety of invertebrates, as well as mammalian and nonmammalian vertebrates. It has been established that the biophysical properties, pharmacology and gene organization of invertebrate sodium channels are largely similar to the vertebrate ones, supporting the view that the ancestral sodium channel was established before the evolutionary separation of the invertebrates from the vertebrates. Although different isoforms of voltage sensitive Na-channels have now been identified the mechanism for persistent current remains controversial. An important yet unanswered question is whether persistent and fast inactivating Na-currents arise from different sets of sodium channels or whether the persistent Na-current results from different gating of the same channel type. The aim of the present review is to discuss the origin and the function of the persistent current, focusing on data derived from an invertebrate animal.