NaV1.8 | sodium voltage-gated channel alpha subunit 10
Family:
Sodium channels
Subgroups:
NaV1.1-1.9
Topology:
Alpha subunits consist of four homologous domains (I-IV) with six transmembrane alpha helices (S1–S6) and a pore-forming loop. One a subunit may associate with 1 or 2 b subunits to make up the channel.
NaV1.8: Background Information
NaV1.8 is expressed specifically in the dorsal root ganglion (DRG), in unmyelinated, small-diameter sensory neurons called C-fibres, and is involved in nociception. C-fibres can be activated by noxious thermal or mechanical stimuli and thus can carry pain messages. The specific location of NaV1.8 in sensory neurons of the DRG may make it a key therapeutic target for the development of new analgesics and the treatment of chronic pain. NaV1.8 is a TTX-resistant sodium channel.
Gene:
SCN10A
Human Protein:
UniProt Q9Y5Y9
Tissue:
Brain (small diameter DRG neurons)
Function/ Application:
Excitability of neurons, nociceptive transmission
Pathology:
Neuropathic pain, Multiple Sclerosis
Accessory subunits:
b1, b2, b3
Interaction:
p11, PDZD2 and syntrophin-associated serine/threonine kinase (SASTK), Contactin, CAP-1A
Modulator:
Tetrodotoxin, lidocaine, benzocaine, A-887826, A-803467
Assays:
Patch Clamp: whole cell, room temperature, State- and use-dependence
Particularities:
NaV channel analysis requires GigaOhm seals and a stable and low access resistance
Recommended Reviews:International Union of Pharmacology. XLVII. Nomenclature and Structure-Function Relationships of Voltage-Gated Sodium Channels. Pharmacol Rev 57: 397–409, Catterall, et al. 2005
Data and Applications
NaV1.8 - I/V Characteristics
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) data and applications:
The CHO cells were kindly provided by Charles River.
hNaV1.8 recorded on the SyncroPatch 384PE (a predecessor model of the SyncroPatch 384). Shown are current responses to increasing voltage steps from -60 to +60 mV (left). Current-voltage plot for an average of 380 cells is shown on the right. Shown are mean of peak amplitudes normalized to the maximum of each cell ± S.E.M. The data was fitted using a Boltzmann equation revealing a Vhalf of activation of -2.7 mV (n = 380), in good agreement with the range found in the literature.
NaV1.8 - State Dependent Inhibition
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) data and applications:
Cells were kindly provided by Charles River.
State dependent inhibition of tetracaine on NaV1.8 currents was investigated. Measured on the SyncroPatch 384PE (a predecessor model of the SyncroPatch 384), the perforated cell patch methodology (Escin) and multi-hole chips were used and compared to single-whole chips. Using a state dependant pulse protocol, the IC50 value determined from the first pulse (C1) was calculated as 54.3 µM (Hill coefficient = 1.50), and from the second pulse (C2) as 1.27 µM (Hill coefficient = 0.62).
NaV1.8 - Voltage Dependent Block by Tetracaine
Patchliner data and applications:
Cells were kindly provided by Millipore.
Recordings were made on the Pachliner. The potency of tetracaine was affected by holding potential, becoming less potent with a more negative holding potential. Average concentration response curve for tetracaine, IC50 = 35 ± 8 μM (n = 3) for Vhold - 90 mV and 74 ± 15 μM (n = 4) for Vhold - 120 mV.
NaV1.8 - Tetracaine Pharmacology
Patchliner data and applications:
Cells were kindly provided by Millipore.
A Raw traces from an exemplar cell recorded on the Patchliner showing inhibition of current by increasing concentrations of tetracaine. Shown are current responses to a single step protocol to 20 mV for 25 ms from a holding potential of -90 mV. Current amplitude was completely recovered upon washout of tetracaine (red trace).
B Timeplot of the experiment.
NaV1.8 - Current-Voltage Relationship
Patchliner data and applications:
Cells were kindly provided by Millipore.
A Raw traces from an exemplar cell recorded on the Patchliner. Shown are current responses to increasing voltage steps from -80 to +60 mV.
B Average current-voltage plot, Vhalf of activation was -9 mV (n = 19).
C Average inactivation plot, Vhalf of inactivation was -24 mV (n = 4). NaV1.8 currents started to activate at about -40 mV, peak response was elicited at around 20 mV.
Webinars and Movies
2018 - Biophysical and Pharmacological Characterization of Voltage-Gated Sodium Channels Involved in Pain Pathways
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i) Oral Presentation Video
Presenter:
Dr. Markus Rapedius, Senior Scientist, Nanion Technologies
Application Notes
NaV1.8 - "Stability and reproducibility of hNaV1.8 recordings on Nanion's SyncroPatch 384PE"
SyncroPatch 384PE (a predecessor model of SyncroPatch 384) application note 
(1.4 MB)
Cells were kindly provided by Charles River.
NaV1.8 - "Characterization of rNaV1.8 (ND7-23) on Nanion's Patchliner"
Patchliner application note: (0.4 MB)
Cells were kindly provided by Millipore.
Posters
2018 - Investigating pain pathways by inhibition of voltage-gated sodium channels
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) and Patchliner poster, FENS Meeting 2018 (2.5 MB)
Publications
2021 - Study of Anti-Inflammatory and Analgesic Activity of Scorpion Toxins DKK-SP1/2 from Scorpion Buthus martensii Karsch (BmK)
Port-a-Patch Publication in Toxins (2021)
Authors:
2020 - Characterization of Vixotrigine, a Broad-Spectrum Voltage-Gated Sodium Channel Blocker
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i instrument) publication in Molecular Pharmacology (2020)
Authors:
A. Hinckley C., Kuryshev Y., Sers A., Barre A., Buisson B., Naik H., Hajos M.
2019 - Fenamates inhibit human sodium channel Nav1.7 and Nav1.8
Port-a-Patch publication in Neuroscience Letters (2019)
Authors:
Sun, J-F., Xu, Y-J., Kong, X-H., Su, Y., Wang, Z-Y.
2018 - The opioid oxycodone use‐dependently inhibits the cardiac sodium channel Nav1.5
CardioExcyte 96 publication in British Journal of Pharmacology (2018)
Authors:
Meents J.E., Juhasz K., Stölzle-Feix S., Peuckmann-Post V., Rolke R. Lampert A.
2017 - A mutant of the Buthus martensii Karsch antitumor-analgesic peptide exhibits reduced inhibition to hNav1.4 and hNav1.5 channels while retaining analgesic activity
Port-a-Patch publication in Journal of Biological Chemistry (2017)
Authors:
Xu Y., Meng X., Hou X., Sun J., Kong X., Sun Y., Liu Z., Ma Y., Niu Y., Song Y., Cui Y., Zhao M., Zhang J.
2012 - Isolation, characterization and total regioselective synthesis of the novel μO-conotoxin MfVIA from Conus magnificus that targets voltage-gated sodium channels
Port-a-Patch publication in Biochemical Pharmacology (2012)
Authors:
Vetter I., Dekan Z., Knapp O., Adams D.J., Alewood P.F., Lewis R.J.