Bruce P. Bean
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View article: Enabling wider access to human molecular neuroscience research in pain: A simple preservation method for human dorsal root ganglion neurons in Hibernate A media
Enabling wider access to human molecular neuroscience research in pain: A simple preservation method for human dorsal root ganglion neurons in Hibernate A media Open
Summary The use of human dorsal root ganglion (DRG) from organ donors opens the door for research into the molecular biology and physiology of human nociceptors; however, there are barriers to working with this tissue including logistical …
View article: Modulation of human dorsal root ganglion neuron firing by the Nav1.8 inhibitor suzetrigine
Modulation of human dorsal root ganglion neuron firing by the Nav1.8 inhibitor suzetrigine Open
Nav1.8 voltage-gated sodium channels are strongly expressed in human primary pain-sensing neurons (nociceptors) and a selective Nav1.8 inhibitor VX-548 (suzetrigine) has shown efficacy for treating acute pain in clinical trials. Nociceptor…
View article: Mechanisms of pacemaking in mammalian neurons
Mechanisms of pacemaking in mammalian neurons Open
Many neurons in the mammalian brain show pacemaking activity: rhythmic generation of action potentials in the absence of sensory or synaptic input. Slow pacemaking of neurons releasing modulatory transmitters is easy to rationalize. More s…
View article: Downregulation of the silent potassium channel Kv8.1 increases motor neuron vulnerability in amyotrophic lateral sclerosis
Downregulation of the silent potassium channel Kv8.1 increases motor neuron vulnerability in amyotrophic lateral sclerosis Open
While voltage-gated potassium channels have critical roles in controlling neuronal excitability, they also have non-ion–conducting functions. Kv8.1, encoded by the KCNV1 gene, is a ‘silent’ ion channel subunit whose biological role is comp…
View article: Cannabidiol inhibits Nav channels through two distinct binding sites
Cannabidiol inhibits Nav channels through two distinct binding sites Open
Cannabidiol (CBD), a major non-psychoactive phytocannabinoid in cannabis, is an effective treatment for some forms of epilepsy and pain. At high concentrations, CBD interacts with a huge variety of proteins, but which targets are most rele…
View article: Downregulation of the silent potassium channel Kv8.1 increases ALS motor neuron vulnerability
Downregulation of the silent potassium channel Kv8.1 increases ALS motor neuron vulnerability Open
The Kv8.1 potassium ion channel encoded by the KCNV1 gene is a “silent” subunit whose biological function is unknown. In ALS patient-derived motor neurons carrying SOD1(A4V) and C9orf72 mutations, its expression is highly reduced, yielding…
View article: Decision letter: A-type FHFs mediate resurgent currents through TTX-resistant voltage-gated sodium channels
Decision letter: A-type FHFs mediate resurgent currents through TTX-resistant voltage-gated sodium channels Open
Article Figures and data Abstract Editor's evaluation Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Resurgent currents (IN…
View article: Scalable Generation of Pseudo-Unipolar Sensory Neurons from Human Pluripotent Stem Cells
Scalable Generation of Pseudo-Unipolar Sensory Neurons from Human Pluripotent Stem Cells Open
Development of new non-addictive analgesics requires advanced strategies to differentiate human pluripotent stem cells (hPSCs) into relevant cell types amenable for translational research. Here, we developed a highly efficient and reproduc…
View article: Cannabidiol activates neuronal Kv7 channels
Cannabidiol activates neuronal Kv7 channels Open
Cannabidiol (CBD), a chemical found in the Cannabis sativa plant, is a clinically effective antiepileptic drug whose mechanism of action is unknown. Using a fluorescence-based thallium flux assay, we performed a large-scale screen and foun…
View article: Author response: Cannabidiol activates neuronal Kv7 channels
Author response: Cannabidiol activates neuronal Kv7 channels Open
Article Figures and data Abstract Editor's evaluation Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Cannabidiol (CBD), a c…
View article: Decision letter: Frequency- and spike-timing-dependent mitochondrial Ca2+ signaling regulates the metabolic rate and synaptic efficacy in cortical neurons
Decision letter: Frequency- and spike-timing-dependent mitochondrial Ca2+ signaling regulates the metabolic rate and synaptic efficacy in cortical neurons Open
Article Figures and data Abstract Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Mitochondrial activity is crucial for the …
View article: Developing nociceptor-selective treatments for acute and chronic pain
Developing nociceptor-selective treatments for acute and chronic pain Open
Phenotypic screens using human induced pluripotent stem cell–derived nociceptors hold promise for the development of better analgesics.
View article: Cannabidiol activates neuronal Kv7 channels
Cannabidiol activates neuronal Kv7 channels Open
Cannabidiol (CBD), a chemical found in the Cannabis sativa plant, is a clinically effective antiepileptic drug whose mechanism of action is unknown. Using a fluorescence-based thallium flux assay, we performed a large-scale screen and foun…
View article: Bidirectional flow of the funny current (I <sub>f</sub> ) during the pacemaking cycle in murine sinoatrial node myocytes
Bidirectional flow of the funny current (I <sub>f</sub> ) during the pacemaking cycle in murine sinoatrial node myocytes Open
Significance The funny current (I f ) is critical for spontaneous activity in cardiac pacemaker cells; however, its precise role remains enigmatic because it activates mostly outside the physiological voltage range and its kinetics are slo…
View article: Cannabidiol Inhibition of Murine Primary Nociceptors: Tight Binding to Slow Inactivated States of Na<sub>v</sub>1.8 Channels
Cannabidiol Inhibition of Murine Primary Nociceptors: Tight Binding to Slow Inactivated States of Na<sub>v</sub>1.8 Channels Open
The nonpsychoactive phytocannabinoid cannabidiol (CBD) has been shown to have analgesic effects in animal studies but little is known about its mechanism of action. We examined the effects of CBD on intrinsic excitability of primary pain-s…
View article: Inhibition of inflammatory pain and cough by a novel charged sodium channel blocker
Inhibition of inflammatory pain and cough by a novel charged sodium channel blocker Open
Background and Purpose Many pain‐triggering nociceptor neurons express TRPV1 or TRPA1, cation‐selective channels with large pores that enable permeation of QX‐314, a cationic analogue of lidocaine. Co‐application of QX‐314 with TRPV1 or TR…
View article: Bi-directional flow of the funny current (I<sub>f</sub>) during the pacemaking cycle in murine sinoatrial node myocytes
Bi-directional flow of the funny current (I<sub>f</sub>) during the pacemaking cycle in murine sinoatrial node myocytes Open
Sinoatrial node myocytes (SAMs) act as cardiac pacemaker cells by firing spontaneous action potentials (APs) that initiate each heartbeat. The funny current, I f , is critical for the generation of these spontaneous APs; however, its preci…
View article: BK Channel Regulation of Afterpotentials and Burst Firing in Cerebellar Purkinje Neurons
BK Channel Regulation of Afterpotentials and Burst Firing in Cerebellar Purkinje Neurons Open
BK calcium-activated potassium channels have complex kinetics because they are activated by both voltage and cytoplasmic calcium. The timing of BK activation and deactivation during action potentials determines their functional role in reg…
View article: Inhibition of inflammatory pain and cough by a novel charged sodium channel blocker
Inhibition of inflammatory pain and cough by a novel charged sodium channel blocker Open
Background and Purpose: Many pain-triggering nociceptor neurons express TRPV1 or TRPA1, cation-selective channels with large pores that enable permeation of QX-314, a cationic analogue of lidocaine. Co-application of QX-314 with TRPV1 or T…
View article: Decision letter: Dyshomeostatic modulation of Ca2+-activated K+ channels in a human neuronal model of KCNQ2 encephalopathy
Decision letter: Dyshomeostatic modulation of Ca2+-activated K+ channels in a human neuronal model of KCNQ2 encephalopathy Open
Article Figures and data Abstract Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Mutations in KCNQ2, which encodes a pore-f…
View article: Inhibiting cough by silencing large pore-expressing airway sensory neurons with a charged sodium channel blocker
Inhibiting cough by silencing large pore-expressing airway sensory neurons with a charged sodium channel blocker Open
Although multiple diseases of the respiratory system cause cough, there are few effective treatments for this common condition. We previously developed a strategy to treat pain and itch via the long-lasting inhibition of nociceptor sensory…
View article: Anthrax Toxin as a Molecular Platform to Target Nociceptive Neurons and Modulate Pain
Anthrax Toxin as a Molecular Platform to Target Nociceptive Neurons and Modulate Pain Open
Bacterial toxins are able to act on neurons to modulate signaling and function. Here, we find that nociceptive sensory neurons that mediate pain are enriched in the receptor for anthrax toxins, ANTXR2. Anthrax Edema Toxin (ET) induced cAMP…