Differential regulation of three sodium channel messenger RNAs in the rat central nervous system during development.

Abstract

The levels of the mRNAs encoding sodium channels I, II and III in various regions of the developing rat central nervous system (from embryonal day 10 to postnatal day 90) have been examined by blot hybridization analysis with specific probes. The three sodium channel mRNAs exhibit different temporal and regional expression patterns. The expression of sodium channel I mRNA rises after a lag phase to adult levels during the second and third postnatal weeks with stronger increases in caudal regions of the brain and in spinal cord. Sodium channel II mRNA increases steadily until the first postnatal week, keeping high adult levels in rostral regions of the brain or reaching low adult levels after the second postnatal week in most caudal regions of the brain and in spinal cord; cerebellum shows low levels during the first two postnatal weeks but high adult levels. In all regions, sodium channel III mRNA attains maximum levels around birth and decreases during the first and second postnatal weeks to reach variable low adult levels. These results suggest that sodium channel III is expressed predominantly at fetal and early postnatal stages and sodium channel I predominantly at late postnatal stages, whereas sodium channel II is expressed throughout the developmental stages studied with greater regional variability.

Altered Sodium Channel Expression in Second-Order Spinal Sensory Neurons Contributes to Pain after Peripheral Nerve Injury

“…Spinal expression of Na v 1.3 is detectable at embryonic day 17 and postnatal day 2 (P2) but is downregulated with further development, exhibiting very low levels of expression by P30 (Beckh et al, 1989;Felts et al, 1997). Upregulation of Na v 1.3 is functionally important because, Na v 1.3 recovers (reprimes) rapidly from inactivation, a property that poises neurons to produce highfrequency activity (Cummins and Waxman, 1997;Black et al, 1999;Cummins et al, 2001).…”

“…The TTX-sensitive (TTX-S) Na v 1.3 sodium channel is normally expressed at relatively high levels in the rat embryonic nervous system but is barely detectable in the adult DRG or spinal cord (Beckh et al, 1989;Waxman et al, 1994;Felts et al, 1997;Hains et al, 2002). However, expression of Na v 1.3 is upregulated within DRG neurons after their axotomy by sciatic nerve transection (Waxman et al, 1994;Black et al, 1999) and after chronic constriction injury (CCI) of the sciatic nerve in adult rats (DibHajj et al, 1999).…”

Fibroblast Growth Factor Homologous Factor 1B Binds to the C Terminus of the Tetrodotoxin-resistant Sodium Channel rNav1.9a (NaN)

“…Heterologous expression of recombinant rNa v 1.9a in HEK293 mammalian cells or DRG neurons in culture for 7 days after biolistic transformation did not show TTX-R currents similar to those observed in vivo. 2 One possibility is that these expression systems may lack a factor(s) that is important for the stability or efficient anchoring of the rNa v 1.9a channels in the membranes of these cells or the modulation of these channels so that they can produce the predicted Na ϩ currents. The expression of the Drosophila sodium channel para in heterologous expression systems is dependent upon the co-expression of tipE factor (49).…”

“…Various ␣-subunits are expressed in a tissue-and developmentally specific manner (2). Aberrant expression patterns or mutations of voltage-gated sodium channel ␣-subunits underlie a number of human and animal disorders (3-7), including neuropathic pain (8,9).…”

Contactin Associates with Sodium Channel Nav1.3 in Native Tissues and Increases Channel Density at the Cell Surface

“…The tetrodotoxin-sensitive (TTX-S) channel Na v 1.3 is abundantly expressed in neuronal tissues during embryonic and neonatal stages of development and is rare in adult tissues (Beckh et al, 1989;Felts et al, 1997;Shah et al, 2001;Lindia and Abbadie, 2003). After axonal transection, Na v 1.3 is upregulated in dorsal root ganglia (DRG) neurons (Waxman et al, 1994;Dib-Hajj et al, 1996;Black et al, 1999;Kim et al, 2001), and a rapidly repriming TTX-S current emerges in these neurons (Cummins and Waxman, 1997).…”