ArticleThe Journal of clinical investigation2017
Sodium channel NaV1.9 mutations associated with insensitivity to pain dampen neuronal excitability.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 89 citations in OpenAlex.
- Comparative Electrophysiological Analysis of Trigeminal and Dorsal Root Ganglion Neurons in Mice.eNeuro · 2026Article
- Functional and molecular diversity of human C-fibers in pain modulation.Current opinion in supportive and palliative care · 2026Review
- High-throughput multiplex voltage-clamp/current-clamp evaluation of acutely isolated neurons.Nature protocols · 2026Review
- Targeting NaInternational journal of molecular sciences · 2026Review
- Shaping the Action Potential in Dorsal Root and Trigeminal Ganglia Neurons: Relevance to Pain Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Development of a Novel Benzodiazepine to Delineate Peripheral GABA-A Signaling Mechanisms in Visceral Pain Syndromes.Cellular and molecular gastroenterology and hepatology · 2026Article
- ER stress-induced ITPR1/ANO1 signaling drives trigeminal neuropathic pain through calcium-dependent neuronal hyperexcitability.The journal of headache and pain · 2025Article
- Familial Episodic Pain Syndrome: A Japanese Family Harboring the Novel Variant c.2431C>T (p.Leu811Phe) in SCN11A.Biochemical genetics · 2025Article
- Sculpting excitable membranes: voltage-gated ion channel delivery and distribution.Nature reviews. Neuroscience · 2025Review
- A robust expression system reveals distinct gating mechanisms and calmodulin regulation of NaScience advances · 2025Article
- Nociceptor sodium channels shape subthreshold phase, upstroke, and shoulder of action potentials.The Journal of general physiology · 2025Article
- Short Peptides from Asian Scorpions: Bioactive Molecules with Promising Therapeutic Potential.Toxins · 2025Review
- Article
- Nav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeted blockade of aberrant sodium current in a stem cell-derived neuron model of SCN3A encephalopathy.Brain : a journal of neurology · 2024Article
- The influence of Nav1.9 channels on intestinal hyperpathia and dysmotility.Channels (Austin, Tex.) · 2023Review
- Peripheral temperature dysregulation associated with functionally altered NaPflugers Archiv : European journal of physiology · 2023Article
- NaExperimental neurology · 2023Article
- Genetic Profiling of Sodium Channels in Diabetic Painful and Painless and Idiopathic Painful and Painless Neuropathies.International journal of molecular sciences · 2023Article
- A TRPM7 mutation linked to familial trigeminal neuralgia: Omega current and hyperexcitability of trigeminal ganglion neurons.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Voltage-gated sodium channel (NaV) mutations cause genetic pain disorders that range from severe paroxysmal pain to a congenital inability to sense pain. Previous studies on NaV1.7 and NaV1.8 established clear relationships between perturbations in channel function and divergent clinical phenotypes. By contrast, studies of NaV1.9 mutations have not revealed a clear relationship of channel dysfunction with the associated and contrasting clinical phenotypes. Here, we have elucidated the functional consequences of a NaV1.9 mutation (L1302F) that is associated with insensitivity to pain. We investigated the effects of L1302F and a previously reported mutation (L811P) on neuronal excitability. In transfected heterologous cells, the L1302F mutation caused a large hyperpolarizing shift in the voltage-dependence of activation, leading to substantially enhanced overlap between activation and steady-state inactivation relationships. In transfected small rat dorsal root ganglion neurons, expression of L1302F and L811P evoked large depolarizations of the resting membrane potential and impaired action potential generation. Therefore, our findings implicate a cellular loss of function as the basis for impaired pain sensation. We further demonstrated that a U-shaped relationship between the resting potential and the neuronal action potential threshold explains why NaV1.9 mutations that evoke small degrees of membrane depolarization cause hyperexcitability and familial episodic pain disorder or painful neuropathy, while mutations evoking larger membrane depolarizations cause hypoexcitability and insensitivity to pain.
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