Journal article
FUNCTIONAL TETRODOTOXIN-RESISTANT Na+ CHANNELS ARE EXPRESSED PRESYNAPTICALLY IN RAT DORSAL ROOT GANGLIA NEURONS
Neuroscience, Vol.159(2), pp.559-569
2009
DOI: 10.1016/j.neuroscience.2008.12.029
PMID: 19162133
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.
Details
- Title: Subtitle
- FUNCTIONAL TETRODOTOXIN-RESISTANT Na+ CHANNELS ARE EXPRESSED PRESYNAPTICALLY IN RAT DORSAL ROOT GANGLIA NEURONS
- Creators
- Y. V MEDVEDEVA - Department of Pharmacology, University of Iowa, Carver College of Medicine, 2-250 BSB, 51 Newton Road, Iowa City, IA 52242, United StatesM-S Kim - Department of Pharmacology, University of Iowa, Carver College of Medicine, 2-250 BSB, 51 Newton Road, Iowa City, IA 52242, United StatesK SCHNIZLER - Department of Pharmacology, University of Iowa, Carver College of Medicine, 2-250 BSB, 51 Newton Road, Iowa City, IA 52242, United StatesY. M USACHEV - Department of Pharmacology, University of Iowa, Carver College of Medicine, 2-250 BSB, 51 Newton Road, Iowa City, IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.159(2), pp.559-569
- Publisher
- Elsevier; Amsterdam
- DOI
- 10.1016/j.neuroscience.2008.12.029
- PMID
- 19162133
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Language
- English
- Date published
- 2009
- Academic Unit
- Iowa Neuroscience Institute; Anesthesia; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
- Record Identifier
- 9984040483902771
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