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- W4386328178 abstract "Abstract Cell-specific alternative splicing of Cacna1b pre-mRNA generates functionally distinct voltage-gated Ca V 2.2 channels. Ca V 2.2 channels mediate the release of glutamate from nociceptor termini in the dorsal horn spinal cord and they are implicated in chronic pain. One alternatively spliced exon in Cacna1b , e37a, is highly expressed in dorsal root ganglia, relative to other regions of the nervous system, and it is particularly important in inflammatory hyperalgesia. Here we studied the effects of two ω-phonetoxins, PnTx3-4 and Phα1β, derived from the spider Phoneutria nigriventer on Ca V 2.2 channel isoforms of dorsal root ganglia (Ca V 2.2 e37a and Ca V 2.2 e37b). Both PnTx3-4 and Phα1β are known to have analgesic effects in rodent models of pain and to inhibit Ca V 2.2 channels. Ca V 2.2 e37a and Ca V 2.2 e37b isoforms expressed in a mammalian cell line were inhibited by PnTx3-4 and Phα1β with similar potency and with similar timecourse, although Ca V 2.2 e37a currents were slightly, but consistently more sensitive to toxin inhibition compared to Ca V 2.2 e37b. The inhibitory effects of PnTx3-4 and Phα1β on Ca V 2.2-e37a and Ca V 2.2-e37b channels were voltage-dependent, and both occlude the inhibitory effects of ω-conotoxin GVIA, consistent with a common site of action. The potency of PnTx3-4 and Phα1β on both major splice isoforms in dorsal root ganglia constribute to understanding the analgesic actions of these ω-phonetoxins." @default.
- W4386328178 created "2023-09-01" @default.
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- W4386328178 date "2023-08-31" @default.
- W4386328178 modified "2023-10-12" @default.
- W4386328178 title "ω-Phonetoxins inhibit voltage-gated calcium CaV2.2 ion channel splice isoforms of dorsal root ganglia" @default.
- W4386328178 doi "https://doi.org/10.1101/2023.08.29.555337" @default.
- W4386328178 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37693414" @default.
- W4386328178 hasPublicationYear "2023" @default.
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