Disease relevance of Scn9a

• Decrease in inflammatory hyperalgesia by herpes vector-mediated knockdown of Nav1.7 sodium channels in primary afferents [1].
• Together, these observations show that PN-1 promotes neurite outgrowth from neuroblastoma cells by inhibiting thrombin and suggest that this depends on the ability of thrombin to retract neurites [2].

Psychiatry related information on Scn9a

• Double knockouts of both Nav1.7 and Nav1.8 also develop normal levels of neuropathic pain, despite a lack of inflammatory pain symptoms and altered mechanical and thermal acute pain thresholds [3].

High impact information on Scn9a

• Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain [4].
• Induction of peripheral inflammation increases the expression of the Nav1.7 sodium channel in sensory neurons, potentially increasing their excitability [1].
• Development of closed-state inactivation was also much faster for Nav1.6 currents than for Nav1.7 currents [5].
• A recent study demonstrated that Nav1.7 expression is negatively correlated with conduction velocity and DRG cell size, while the Nav1.6 voltage-gated sodium channel has been implicated as the predominant isoform present at nodes of Ranvier of myelinated fibres [5].
• Among subpopulations of granulosa cells, the expression of PN-1 and uPA was heterogeneous and complementary [6].

Biological context of Scn9a

• Linkage analysis established that Scn9a mapped to the proximal segment of mouse chromosome 2 [7].
• Distinct repriming and closed-state inactivation kinetics of Nav1.6 and Nav1.7 sodium channels in mouse spinal sensory neurons [5].
• In LRP1-/- MEF cells, inhibitor sensitivity and kinetic values (t(1/2) at 45 min) of PN-1 uptake showed a similarity to syndecan-1-mediated endocytosis [8].
• In these cells, PN-1 uptake was increased by overexpression of full-length syndecan-1 and decreased by RNA interference targeting this proteoglycan [8].
• Protease nexin-1 (PN-1), an inhibitor of serine proteases, contributes to tissue homeostasis and influences the behavior of some tumor cells [8].

Anatomical context of Scn9a

• We have used a total of 27 AXB/BXA recombinant inbred mouse strains to determine the chromosomal location of a newly identified gene encoding an alpha-subunit isoform of the sodium channel from Schwann cells, Scn9a [7].
• To test whether NT-3 could prevent muscle spindle degeneration, spindle number and morphology were assessed 3 weeks after sciatic nerve crush or section on PN1 [9].
• Mis-expression of voltage-gated sodium channels by damaged sensory neurons has also been implicated in the development of neuropathic pain, but the role of Nav1.7 and Nav1.8 is uncertain [3].
• Two voltage gated sodium channel alpha-subunits, Nav1.7 and Nav1.8, are expressed at high levels in nociceptor terminals and have been implicated in the development of inflammatory pain [3].
• It has been suggested that PN-1:thrombin complexes might mediate the neurite outgrowth activity of PN-1 [2].

Associations of Scn9a with chemical compounds

• In contrast, ACh treatment in the presence of TTX had no effect on PN1 gene expression compared to treatment with TTX alone [10].

Other interactions of Scn9a

• The segregation of restriction fragment length polymorphisms in 145 progeny from a Mus spretus x C57BL/6J backcross indicates that Scn9a is very tightly linked to Scn1a (gene encoding the type I sodium channel alpha-subunit of the brain) and forms part of a cluster of four Scna genes located on mouse chromosome 2 [7].
• Genetic mapping of the peripheral sodium channel genes, Scn9a and Scn10a, in the mouse [11].

Analytical, diagnostic and therapeutic context of Scn9a

• The changes in mRNA levels of the three genes after denervation indicated that these genes were regulated in a innervation-dependent manner and that nerve activity may play an important regulatory role in the expression of prothrombin, ThR, and PN-1 [12].

References