Dataset Information

Fatty Acid and Related Potassium Kv2 Channel Blockers: Toxicity and Physiological Actions on Mosquitoes.

ABSTRACT: Potassium channels constitute a very diverse group involved in neural signaling, neuronal activity, membrane potential maintenance, and action potential generation. Here, we tested the mammalian potassium channel blockers TRAM-34 and 5-hydroxydecanoate (5-HDC), as well as certain fatty acids (FA) that might fit in the lumen of the pore and block channel activity by obstructing K? ion passage. Kv channel blockers could be leads for a novel pesticide type. Insecticidal activity was assessed by topical application to Anopheles gambiae adult mosquitoes, paralysis in a headless larval assay, at the cellular level with patch-clamp recordings of engineered HEK cells expressing AgKv2.1 channels, as well as central nervous system recordings from larval Drosophila melanogaster. With only one hydroxyl group difference, decanoic acid had a consistently greater effect than 5-HDC in blocking Kv channels, paralyzing larvae, and killing mosquitoes. The 11-dansylamino undecanoic acid (DAUDA) blockage of eukaryotic Kv channels is demonstrated for the first time, but it failed to kill adult mosquitoes. We synthesized alkyl esters from DAUDA and decanoic acid in an effort to improve cuticular penetration, but it had little impact upon adult toxicity. TRAM-34 and rolipram did not show activity on Kv channels nor potent insecticidal effect on adult mosquitoes. Furthermore, co-application of test compounds with permethrin did not increase mortality in adults. In conclusion, the compounds tested had modest insecticidal and synergistic activity.

SUBMITTER: Demares F

PROVIDER: S-EPMC6315728 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fatty Acid and Related Potassium Kv2 Channel Blockers: Toxicity and Physiological Actions on Mosquitoes.

Démares Fabien F Coquerel Quentin Q Richoux Gary G Linthicum Kenneth K Bloomquist Jeffrey J

Insects 20181101 4

Potassium channels constitute a very diverse group involved in neural signaling, neuronal activity, membrane potential maintenance, and action potential generation. Here, we tested the mammalian potassium channel blockers TRAM-34 and 5-hydroxydecanoate (5-HDC), as well as certain fatty acids (FA) that might fit in the lumen of the pore and block channel activity by obstructing K⁺ ion passage. Kv channel blockers could be leads for a novel pesticide type. Insecticidal activity was assessed by top ...[more]

PMID: 30388752

Similar Datasets

Project description:Silent voltage-gated potassium channel subunits (KVS) interact selectively with members of the KV2 channel family to modify their functional properties. The localization and functional roles of these silent subunits remain poorly understood. Mutations in the KVS subunit, KV8.2 (KCNV2), lead to severe visual impairment in humans, but the basis of these deficits remains unclear. Here, we examined the localization, native interactions, and functional properties of KV8.2-containing channels in mouse, macaque, and human photoreceptors of either sex. In human retina, KV8.2 colocalized with KV2.1 and KV2.2 in cone inner segments and with KV2.1 in rod inner segments. KV2.1 and KV2.2 could be coimmunoprecipitated with KV8.2 in retinal lysates indicating that these subunits likely interact directly. Retinal KV2.1 was less phosphorylated than cortical KV2.1, a difference expected to alter the biophysical properties of these channels. Using voltage-clamp recordings and pharmacology, we provide functional evidence for Kv2-containing channels in primate rods and cones. We propose that the presence of KV8.2, and low levels of KV2.1 phosphorylation shift the activation range of KV2 channels to align with the operating range of rod and cone photoreceptors. Our data indicate a role for KV2/KV8.2 channels in human photoreceptor function and suggest that the visual deficits in patients with KCNV2 mutations arise from inadequate resting activation of KV channels in rod and cone inner segments.SIGNIFICANCE STATEMENT Mutations in a voltage-gated potassium channel subunit, KV8.2, underlie a blinding inherited photoreceptor dystrophy, indicating an important role for these channels in human vision. Here, we have defined the localization and subunit interactions of KV8.2 channels in primate photoreceptors. We show that the KV8.2 subunit interacts with different Kv2 channels in rods and cones, giving rise to potassium currents with distinct functional properties. Our results provide a molecular basis for retinal dysfunction in patients with mutations in the KCNV2 gene encoding KV8.2.

Dataset Information

Fatty Acid and Related Potassium Kv2 Channel Blockers: Toxicity and Physiological Actions on Mosquitoes.

Publications

Fatty Acid and Related Potassium Kv2 Channel Blockers: Toxicity and Physiological Actions on Mosquitoes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets