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

Abstract

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.

• Authors: Y V Medvedeva, M-S Kim, K Schnizler, Y M Usachev
• Journal: Neuroscience (Neuroscience) Vol. 159 Issue 2 Pg. 559-69 (Mar 17 2009) ISSN: 0306-4522 [Print] United States
• PMID: 19162133 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics, Local
• Benzofurans
• Disks Large Homolog 4 Protein
• Dlg4 protein, rat
• Ethers, Cyclic
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• NAV1.8 Voltage-Gated Sodium Channel
• NAV1.9 Voltage-Gated Sodium Channel
• Nerve Tissue Proteins
• Neuropeptides
• Scn10a protein, rat
• Scn11a protein, rat
• Sodium Channel Blockers
• Sodium Channels
• sodium-binding benzofuran isophthalate
• Tetrodotoxin
• Lidocaine
• Sodium
• Calcium

Topics

• Action Potentials (drug effects, physiology)
• Anesthetics, Local (pharmacology)
• Animals
• Animals, Newborn
• Benzofurans (metabolism)
• Biophysics
• Calcium (metabolism)
• Cells, Cultured
• Coculture Techniques
• Disks Large Homolog 4 Protein
• Electric Stimulation
• Ethers, Cyclic (metabolism)
• Extracellular Fluid (drug effects, metabolism)
• Ganglia, Spinal (cytology)
• Intracellular Signaling Peptides and Proteins (metabolism)
• Ion Channel Gating (drug effects)
• Lidocaine (pharmacology)
• Membrane Proteins (metabolism)
• NAV1.8 Voltage-Gated Sodium Channel
• NAV1.9 Voltage-Gated Sodium Channel
• Nerve Tissue Proteins (metabolism)
• Neuropeptides (metabolism)
• Patch-Clamp Techniques (methods)
• Presynaptic Terminals (metabolism)
• Rats
• Rats, Sprague-Dawley
• Sensory Receptor Cells (cytology, drug effects)
• Sodium (metabolism)
• Sodium Channel Blockers (pharmacology)
• Sodium Channels (drug effects, metabolism)
• Spinal Cord (cytology)
• Synapses (drug effects, physiology)
• Tetrodotoxin (pharmacology)