Jeff S. McDermott
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View article: Expression and localization of NMDA receptor GluN2 subunits in dorsal horn pain circuits across sex, species, and late postnatal development
Expression and localization of NMDA receptor GluN2 subunits in dorsal horn pain circuits across sex, species, and late postnatal development Open
Despite being essential mediators of pain processing, the molecular identity of N-methyl-D-aspartate receptor (NMDAR) subtypes in nociceptive dorsal horn circuits is poorly understood, especially between sexes and in humans. Given the impo…
View article: Processing and sectioning of organ donor spinal cord tissue for electrophysiology on acute human spinal cord slices
Processing and sectioning of organ donor spinal cord tissue for electrophysiology on acute human spinal cord slices Open
Acute spinal cord slice electrophysiology is a powerful technique used in preclinical basic science research to investigate sensory and motor neuron function and pathophysiology. A major barrier that stands between implementing these findi…
View article: Stimulus intensity-dependent recruitment of Na<sub>V</sub>1 subunits in action potential initiation in nerve terminals of vagal C-fibers innervating the esophagus
Stimulus intensity-dependent recruitment of Na<sub>V</sub>1 subunits in action potential initiation in nerve terminals of vagal C-fibers innervating the esophagus Open
We report that pharmacologically distinguishable voltage-gated sodium channels (Na V 1) mediate action potential initiation at low (innocuous) versus high (noxious) intensity of esophageal distention in nerve terminals of vagal nodose C-fi…
View article: Preferential Pharmacological Inhibition of Nav1.6, but not Nav1.1, Abolishes Epileptiform Activity Induced by 4-AP in Mouse Cortical Slices
Preferential Pharmacological Inhibition of Nav1.6, but not Nav1.1, Abolishes Epileptiform Activity Induced by 4-AP in Mouse Cortical Slices Open
Brain isoforms of voltage-gated sodium channels (VGSCs) have distinct cellular and subcellular expression patterns as well as functional roles that are critical for normal physiology as aberrations in their expression or activity lead to p…
View article: Extracellular signal-regulated kinases mediate the enhancing effects of inflammatory mediators on resurgent currents in dorsal root ganglion neurons
Extracellular signal-regulated kinases mediate the enhancing effects of inflammatory mediators on resurgent currents in dorsal root ganglion neurons Open
Previously we reported that a group of inflammatory mediators significantly enhanced resurgent currents in dorsal root ganglion neurons. To understand the underlying intracellular signaling mechanism, we investigated the effects of inhibit…
View article: Targeting the Nerve Growth Factor (NGF) Pathway in Drug Discovery. Potential Applications to New Therapies for Chronic Pain
Targeting the Nerve Growth Factor (NGF) Pathway in Drug Discovery. Potential Applications to New Therapies for Chronic Pain Open
The neurotrophin nerve growth factor (NGF) has been implicated as a key mediator of chronic pain. NGF binds the tropomysin receptor kinase A (TrkA) and p75, resulting in the activation of downstream signaling pathways that have been linked…
View article: Sulfonamides as Selective Na<sub>V</sub>1.7 Inhibitors: Optimizing Potency and Pharmacokinetics to Enable in Vivo Target Engagement
Sulfonamides as Selective Na<sub>V</sub>1.7 Inhibitors: Optimizing Potency and Pharmacokinetics to Enable in Vivo Target Engagement Open
Human genetic evidence has identified the voltage-gated sodium channel NaV1.7 as an attractive target for the treatment of pain. We initially identified naphthalene sulfonamide 3 as a potent and selective inhibitor of NaV1.7. Optimization …
View article: Inhibition of Inactive States of Tetrodotoxin-Sensitive Sodium Channels Reduces Spontaneous Firing of C-Fiber Nociceptors and Produces Analgesia in Formalin and Complete Freund’s Adjuvant Models of Pain
Inhibition of Inactive States of Tetrodotoxin-Sensitive Sodium Channels Reduces Spontaneous Firing of C-Fiber Nociceptors and Produces Analgesia in Formalin and Complete Freund’s Adjuvant Models of Pain Open
While genetic evidence shows that the Nav1.7 voltage-gated sodium ion channel is a key regulator of pain, it is unclear exactly how Nav1.7 governs neuronal firing and what biophysical, physiological, and distribution properties of a pharma…
View article: Cardiac ion channels
Cardiac ion channels Open
Ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Consequently, ion channels are key targets for therapeutics aimed at cardiac pathophysiologies such as atrial fibrillation or angina. A…