Logged in as a Visitor.
sodium channel, voltage-gated, type II, alpha 1
Navα1.2, also known as the sodium channel, voltage-gated, type II, alpha subunit is a protein that in humans is encoded by the SCN2A gene. Functional sodium channels contain an ion conductive alpha subunit and one or more regulatory beta subunits. Sodium channels which contain the Navα1.2 subunit are called Nav1.2 channels.
Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. It is heterogeneously expressed in the brain, and mutations in this gene have been linked to several seizure disorders. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.
Different mutants of SCN2A, the gene encoding Nav1.2, show the following behaviour: R1319Q displays mixed effects on activation and fast inactivation gating, consistent with a net loss of channel function. L1563V exhibits impaired fast inactivation predicting a net gain of channel function. The L1330F mutation significantly decrease overall channel availability during repetitive stimulation. Cells expressing BFNIS mutants exhibit lower levels of sodium current compared to wild type (WT) NaV1.2. All three BFNIS mutations exhibit a significant reduction in cell surface expression compared to WT.
Scn2a1 : sodium channel, voltage-gated, type II, alpha 1
BmK AS, a β-like scorpion toxin, causes rNav1.2 α-subunit expressed in Xenopus laevis oocytes to shift the voltage dependence of rNav1.2 inactivation significantly towards positive membrane potential by 500 nM BmK AS. Whereas the activation curves of rNav1.2 were unaffected at the same dosage. The inactivation curves of both slow and fast inactivation currents were positively moved about 12.8 and 9.7 mV, respectively. The persistent currents of rNav1.2 were invariable and the effects of BmK AS on the rNav1.2 inactivation were opposite to the previous results found in the peripheral sensory neurons.
BmK I on rNav1.2a expressed in Xenopus oocytes showed that BmK I prevented the development of slow inactivation of rNav1.2a from the open-state and enhanced the persistent sodium current (INaP) at suprathreshold potentials in concentration-dependence, whereas it hardly affected the fast inactivation. BmK I was also able to augment the subthreshold INaP at high concentrations (>100 nM) with disruption of the open-state deactivation. The increased INaP accelerated the firing frequency in the oocytes that fired repetitively after electrode punctures, as well as raised the baseline potential and induced bursting of spikes in the quiescent oocytes. BmK I could target rNav1.2a and induce the INaP by preventing the development of slow inactivation and deactivation from the open-state, leading to the enhancement of membrane excitability, which may be involved in the BmK I-induced epilepsy.
Ankyrin G acting together with the AIS motif are most likely the primary actors in anchoring sodium channels at the plasma membrane.
II-III Linker Protein
The C terminus of Nav1.2 does not contain sufficient information for sodium channel localization at the AIS, but the II-III linker is critical for sodium channel organization at the AIS. 
Beta 1 Subunit
Relative to NaV1.2 alone, NaV1.2 + beta 1 currents had right-shifted voltage dependence of activation, fast and slow inactivation and reduced use dependence. In addition, the NaV1.2 + beta 1 current entered fast inactivation slightly faster than NaV1.2 channels alone.
Chloramine T enhances the open probability of sodium channels by interfering with the inactivation process.
Phosphorilating Protein Kinases
There are 15 phosphorylation sites on Nav1.2. Extensive modulation of Nav channel activity by phosphorylation in rat brain was found. 
Nav1.2 is TTX sensitive 
In CNS, Nav1.2 is primarily expressed in unmyelinated axons and dendrites . Besides other voltage gated sodium channels but predominately, Nav1.2 and Nav1.6 subunits are co-expressed within a single hair cell.. Nav1.2 can be found at most AIS of CG cells from 8 days in vitro DIV 8 to DIV 15.. At DIV 7–8 Nav1.2 was concentrated at AIS cultured CG cells and colocalized with ankyrin-G and PanNav, suggesting that the high density of Na+ channels at the AIS is mainly due to Nav1.2. 
Sodium channels Nav1.2, are not detectable in the cultured microglia above background levels. 
Nav1.2 expression increases during the third postnatal week, but then continues to increase until reaching maximal levels during adulthood .
Nav1.2 is the most abundant alpha-subunit expressed in the central nervous system, comprising approximately 70% of the total rat brain Nav alpha subunit pool.It is abundantly expressed in axons in the adult CNS, particularly in cortex, thalamus, globus pallidus and hippocampus (mossy fibers, stratum radiatum, stratum oriens). In the cerebellum Nav1.2 is expressed in both Purkinje and granule cells .
Early in development, Nav1.2 is highly expressed in regions destined to become nodes of Ranvier and is replaced during development by NaV1.6 .
Somatic Na+ current in CG cells is dominated by fast gating channels, consistent with the contribution of Nav1.2 and/or Nav1.6. 
Although there are obvious electrophysiological differences between Purkinje cells from rats and Purkinje cells from mormyrid fish, no differences in the expression pattern of Nav1.1, Nav1.2, or Nav1.6 subunits or in fast inactivating or resurgent Na+ currents were detected. Rat and mormyrid Purkinje cells show no differences in their ability to activate Na+ conductances at high enough frequencies to support complex spike firing.
Developmentally regulated NaV1.2 splicing may be one mechanism that counters the normally high excitability of neonatal neurons and helps to reduce seizure susceptibility in normal human infants.
NaV1.2 are regulated by neutrotransmitters that act through G-protein coupled receptors and activate protein kinase A such dopamine, acetylcholine and serotonin (reviewed in Cantrell & Catterall, 2001). 
Several studies have demonstrated that either gain- or loss-of-function mutations of NaV1.2 are associated with disease:
NaV1.2 knockout mice die perinatally from neuronal apoptosis and hypoxia:
Four-mode gating model of fast inactivation of sodium channel Nav1.2a
Chloramine T-induced modification of inactivation is modelled in four steps (=modes) with equal temporal sequence:
Modes 1 and 2: transient defects in the locking of the inactivation particle (hinged lid)
Mode 3: hinged lid beeing unable to lock permanently
Mode 4: the apparent singlechannel current was reduced, which could be explained by fast gating, presumably related to the selectivity filter. 
Editor : Admin.
Contributors : Rajnish Ranjan, Michael Schartner
To cite : [Editor], [Contributors]. Accessed on [Date] Channelpedia , http://channelpedia.epfl.ch/ionchannels/121