Glycosylation Alters Steady-State Inactivation of Sodium Channel Nav1.9/NaN in Dorsal Root Ganglion Neurons and Is Developmentally Regulated

Na channel NaN (Nav1.9) produces a persistent TTX-resistant (TTX-R) current in small-diameter neurons of dorsal root ganglia (DRG) and trigeminal ganglia. Nav1.9-specific antibodies react in immunoblot assays with a 210 kDa protein from the membrane fractions of adult DRG and trigeminal ganglia. The size of the immunoreactive protein is in close agreement with the predicted Nav1.9 theoretical molecular weight of 201 kDa, suggesting limited glycosylation of this channel in adult tissues. Neonatal rat DRG membrane fractions, however, contain an additional higher molecular weight immunoreactive protein. Reverse transcription-PCR analysis did not show additional longer transcripts that could encode the larger protein. Enzymatic deglycosylation of the membrane preparations converted both immunoreactive proteins into a single faster migrating band, consistent with two states of glycosylation of Nav1.9. The developmental change in the glycosylation state of Nav1.9 is paralleled by a developmental change in the gating of the persistent TTX-R Na+ current attributable to Nav1.9 in native DRG neurons. Whole-cell patch-clamp analysis demonstrates that the midpoint of steady-state inactivation is shifted 7 mV in a hyperpolarized direction in neonatal (postnatal days 0–3) compared with adult DRG neurons, although there is no significant difference in activation. Pretreatment of neonatal DRG neurons with neuraminidase causes an 8 mV depolarizing shift in the midpoint of steady-state inactivation of Nav1.9, making it indistinguishable from that of adult DRG neurons. Our data show that extensive glycosylation of rat Nav1.9 is developmentally regulated and changes a critical property of this channel in native neurons.

• Publication year

  2001

• Venue

  Journal of Neuroscience

• Publication date

  2001-12-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1523/JNEUROSCI.21-24-09629.2001PMID 11739573PMCID PMC6763018
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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