RGD Reference Report - Functional tetrodotoxin-resistant Na(+) channels are expressed presynaptically in rat dorsal root ganglia neurons. - Rat Genome Database

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Functional tetrodotoxin-resistant Na(+) channels are expressed presynaptically in rat dorsal root ganglia neurons.

Authors: Medvedeva, Y V  Kim, M-S  Schnizler, K  Usachev, Y M 
Citation: Medvedeva YV, etal., Neuroscience. 2009 Mar 17;159(2):559-69. doi: 10.1016/j.neuroscience.2008.12.029. Epub 2008 Dec 30.
RGD ID: 13702365
Pubmed: PMID:19162133   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuroscience.2008.12.029   (Journal Full-text)

The tetrodotoxin-resistant (TTX-R) voltage-gated Na(+) channels Na(v)1.8 and Na(v)1.9 are expressed by a subset of primary sensory neurons and have been implicated in various pain states. Although recent studies suggest involvement of TTX-R Na(+) channels in sensory synaptic transmission and spinal pain processing, it remains unknown whether TTX-R Na(+) channels are expressed and function presynaptically. We examined expression of TTX-R channels at sensory synapses formed between rat dorsal root ganglion (DRG) and spinal cord (SC) neurons in a DRG/SC co-culture system. Immunostaining showed extensive labeling of presynaptic axonal boutons with Na(v)1.8- and Na(v)1.9-specific antibodies. Measurements using the fluorescent Na(+) indicator SBFI demonstrated action potential-induced presynaptic Na(+) entry that was resistant to tetrodotoxin (TTX) but was blocked by lidocaine. Furthermore, presynaptic [Ca(2+)](i) elevation in response to a single action potential was not affected by TTX in TTX-resistant DRG neurons. Finally, glutamatergic synaptic transmission was not inhibited by TTX in more than 50% of synaptic pairs examined; subsequent treatment with lidocaine completely blocked these TTX-resistant excitatory postsynaptic currents. Taken together, these results provide evidence for presynaptic expression of functional TTX-R Na(+) channels that may be important for shaping presynaptic action potentials and regulating transmitter release at the first sensory synapse.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glutamatergic synapse is_active_inIDA 13702365; 13702365PMID:19162133SynGO 
presynaptic membrane is_active_inIDA 13702365; 13702365PMID:19162133SynGO 

Objects Annotated

Genes (Rattus norvegicus)
Scn10a  (sodium voltage-gated channel alpha subunit 10)
Scn11a  (sodium voltage-gated channel alpha subunit 11)


Additional Information