Pyrethroids inhibit K2P channels and activate sensory neurons: basis of insecticide-induced paraesthesias

Castellanos, Aida; Andres, Alba; Bernal, Laura; Callejo, Gerard; Comes, Núria; Gual, Arcadi; Giblin, Jonathan P.; Roza, Carolina; Gasull, Xavier

doi:10.1097/j.pain.0000000000001068

Cited by 25 publications

(35 citation statements)

References 47 publications

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“…; Castellanos et al . ) or with the decreased excitability when overexpressing the channel (Guo & Cao, ; Yang et al . ), indicating that the regulation of TRESK expression is an important factor to control sensory neuron excitability.…”

Section: Discussionmentioning

confidence: 99%

“…; Castellanos et al . ). The von Frey filaments [size: 2.44, 2.83, 3.22, 3.61, 3.84, 4.08, 4.17, 4.31 and 4.56; equivalent to (in grams) 0.04, 0.07, 0.16, 0.4, 0.6, 1, 1.4, 2 and 4] were applied perpendicularly to the plantar surface of the hind paw and gently pushed to the bending point for 5 s. The 50% withdrawal threshold was determined using the up and down method (Chaplan et al .…”

Section: Methodsmentioning

confidence: 97%

“…, ; Castellanos et al . ). Briefly, recordings were performed with a patch‐clamp amplifier (Axopatch 200B, Molecular Devices) and restricted to small DRG neurons (<30 µm soma diameter), which largely correspond to nociceptive neurons (Le Pichon & Chesler, ).…”

Section: Methodsmentioning

confidence: 97%

“…Mechanical sensitivity of WT and TRESK KO mice was assessed using the 'up and down' method by the application of calibrated von Frey filaments (North Coast Medical, Inc., Morgan Hill, CA, USA) as previously described (Tulleuda et al 2011;Castellanos et al 2018). The von Frey filaments [size: 2.44, 2.83, 3.22, 3.61, 3.84, 4.08, 4.17, 4.31 and 4.56; equivalent to (in grams) 0.04, 0.07, 0.16, 0.4, 0.6, 1, 1.4, 2 and 4] were applied perpendicularly to the plantar surface of the hind paw and gently pushed to the bending point for 5 s. The 50% withdrawal threshold was determined using the up and down method (Chaplan et al 1994).…”

Section: Mouse Mechanical Sensitivitymentioning

confidence: 99%

“…Electrophysiological recordings in DRG sensory neurons were performed as previously described (Callejo et al 2013(Callejo et al , 2015Castellanos et al 2018). Briefly, recordings were performed with a patch-clamp amplifier (Axopatch 200B, Molecular Devices) and restricted to small DRG neurons (<30 µm soma diameter), which largely correspond to nociceptive neurons (Le Pichon & Chesler, 2014).…”

Section: Electrophysiological Recordingmentioning

confidence: 99%

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TRESK background K⁺ channel deletion selectively uncovers enhanced mechanical and cold sensitivity

Castellanos

Pujol-Coma

Andrés‐Bilbé

et al. 2020

The Journal of Physiology

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Key points TRESK background K+ channel is expressed in sensory neurons and acts as a brake to reduce neuronal activation. Deletion of the channel enhances the excitability of nociceptors. Skin nociceptive C‐fibres show an enhanced activation by cold and mechanical stimulation in TRESK knockout animals. Channel deletion selectively enhances mechanical and cold sensitivity in mice, without altering sensitivity to heat. These results indicate that the channel regulates the excitability of specific neuronal subpopulations involved in mechanosensitivity and cold‐sensing. Abstract Background potassium‐permeable ion channels play a critical role in tuning the excitability of nociceptors, yet the precise role played by different subsets of channels is not fully understood. Decreases in TRESK (TWIK‐related spinal cord K+ channel) expression/function enhance excitability of sensory neurons, but its role in somatosensory perception and nociception is poorly understood. Here, we used a TRESK knockout (KO) mouse to address these questions. We show that TRESK regulates the sensitivity of sensory neurons in a modality‐specific manner, contributing to mechanical and cold sensitivity but without any effect on heat sensitivity. Nociceptive neurons isolated from TRESK KO mice show a decreased threshold for activation and skin nociceptive C‐fibres show an enhanced activation by cold and mechanical stimulation that was also observed in behavioural tests in vivo. TRESK is also involved in osmotic pain and in early phases of formalin‐induced inflammatory pain, but not in the development of mechanical and heat hyperalgesia during chronic pain. In contrast, mice lacking TRESK present cold allodynia that is not further enhanced by oxaliplatin. In summary, genetic removal of TRESK uncovers enhanced mechanical and cold sensitivity, indicating that the channel regulates the excitability of specific neuronal subpopulations involved in mechanosensitivity and cold‐sensing, acting as a brake to prevent activation by innocuous stimuli.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 97%

Section: Mouse Mechanical Sensitivitymentioning

confidence: 99%

Section: Electrophysiological Recordingmentioning

confidence: 99%

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TRESK background K⁺ channel deletion selectively uncovers enhanced mechanical and cold sensitivity

Castellanos

Pujol-Coma

Andrés‐Bilbé

et al. 2020

The Journal of Physiology

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Identification and pharmacological characterization of the voltage‐gated potassium channel Shab in diamondback moth, Plutella xylostella

Huo

Zhu

et al. 2022

Pest Management Science

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Background: Voltage-gated potassium channel Kv2 is the primarily delayed rectifier in insect nerves and muscles involved in several crucial biological processes, including action potential regulation, photoreceptor performance, and larval locomotor. It is a potential molecular target for developing a novel pesticide for mosquitos. However, there are few studies on the Kv2 channel in agricultural pests.Results: The only ⊍-subunit gene of the Kv2 channel in Plutella xylostella (L.), PxShab, was cloned, and its expression profile was analyzed. The relative expression level of PxShab was highest in the pupal stage of both sexes and male adults but lowest in female adults. Meanwhile, PxShab had the highest expression in the head in both larvae and adults. Then, PxShab was stably expressed in the HEK-293 T cell line. Whole cell patch clamp recordings showed an outward current whose current-voltage relationship conformed to a typical delayed-rectifier potassium channel. 20 ∼M quinidine could effectively inhibit the potassium current, while the channel was insensitive to 4-AP even at 10 mM. Several potential compounds and botanical pesticides were assessed, and carvedilol (IC 50 = 0.53 ∼M) and veratrine (IC 50 = 2.22 ∼M) had a good inhibitory effect on the channel. Conclusion:This study revealed the pharmacological properties of PxShab and screened out several high potency inhibitors, which laid the foundation for further functional research of PxShab and provides new insight into designing novel insecticides.

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Infections and Infestations

Asz-Sigall¹,

Martínez‐Velasco²,

Arenas

2019

Hair and Scalp Treatments

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Pyrethroids inhibit K2P channels and activate sensory neurons: basis of insecticide-induced paraesthesias

Abstract: Supplemental Digital Content is Available in the Text.Inhibition of K2P potassium channels by pyrethroid insecticides contribute to activate primary sensory neurons to cause paraesthesias and painful sensations.

Cited by 25 publications

References 47 publications

TRESK background K⁺ channel deletion selectively uncovers enhanced mechanical and cold sensitivity

TRESK background K⁺ channel deletion selectively uncovers enhanced mechanical and cold sensitivity

Identification and pharmacological characterization of the voltage‐gated potassium channel Shab in diamondback moth, Plutella xylostella

Infections and Infestations

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Pyrethroids inhibit K2P channels and activate sensory neurons: basis of insecticide-induced paraesthesias

Abstract: Supplemental Digital Content is Available in the Text.Inhibition of K2P potassium channels by pyrethroid insecticides contribute to activate primary sensory neurons to cause paraesthesias and painful sensations.

Cited by 25 publications

References 47 publications

TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity

TRESK background K+ channel deletion selectively uncovers enhanced mechanical and cold sensitivity

Identification and pharmacological characterization of the voltage‐gated potassium channel Shab in diamondback moth, Plutella xylostella

Infections and Infestations

Contact Info

Product

Resources

About

TRESK background K⁺ channel deletion selectively uncovers enhanced mechanical and cold sensitivity

TRESK background K⁺ channel deletion selectively uncovers enhanced mechanical and cold sensitivity