Heterologous expression and functional analysis of rat Nav1.8 (SNS) voltage-gated sodium channels in the dorsal root ganglion neuroblastoma cell line ND7-23
| Autor: | Caroline Anne Hick, Jeffrey J. Clare, Victoria H John, Derek J. Trezise, Harjeet S Sidhu, Martin J. Main, Andrew J. Powell, Simon Tate, Zoe Gladwell |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Nerve Tissue Proteins Gating Sodium Channels Cell Line Membrane Potentials NAV1.8 Voltage-Gated Sodium Channel Rats Sprague-Dawley Cellular and Molecular Neuroscience Neuroblastoma Dorsal root ganglion Cell Line Tumor Ganglia Spinal medicine Animals Humans Pharmacology Membrane potential Chemistry Sodium channel medicine.disease Cell biology Rats Electrophysiology medicine.anatomical_structure Gene Expression Regulation Cell culture Female Heterologous expression Neuroscience Sodium Channel Blockers |
| Zdroj: | Neuropharmacology. 46(3) |
| ISSN: | 0028-3908 |
| Popis: | The voltage-gated sodium channel NaV1.8 (SNS, PN3) is thought to be a molecular correlate of the dorsal root ganglion (DRG) tetrodotoxin resistant (TTX-R) Na+ current. TTX-R/NaV1.8 is an attractive therapeutic drug target for inflammatory and neuropathic pain on the basis of its specific distribution in sensory neurones and its modulation by inflammatory mediators. However, detailed analysis of recombinant NaV1.8 has been hampered by difficulties in stably expressing the functional protein in mammalian cells. Here, we show stable expression and functional analysis of rat NaV1.8 (rNaV1.8) in the rat DRG/mouse N18Tg2 neuroblastoma hybridoma cell line ND7-23. Rat NaV1.8 Na+ currents were recorded (789 +/- 89 pA, n=62, over 20-cell passages) that qualitatively resembled DRG TTX-R in terms of gating kinetics and voltage-dependence of activation and inactivation. The local anaesthetic drug tetracaine produced tonic inhibition of rNaV1.8 (mean IC50 value 12.5 microM) and in repeated gating paradigms (2-10 Hz) also showed frequency-dependent block. There was a correlation between the ability of several analogues of the anticonvulsant/analgesic compound lamotrigine to inhibit TTX-R and rNaV1.8 (r=0.72, P |
| Databáze: | OpenAIRE |
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