{"doi":"10.1101/2023.08.29.555337","title":"ω-Phonetoxins inhibit voltage-gated calcium Ca <sub>V</sub> 2.2 ion channel splice isoforms of dorsal root ganglia","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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":410981,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1191133,"name":"Marcus V. Gomez","orcid":"0000-0002-6082-930X","position":1,"is_corresponding":false},{"id":1191134,"name":"Márcia Helena Borges","orcid":"0000-0001-7848-5632","position":2,"is_corresponding":false},{"id":418309,"name":"Diane Lipscombe","orcid":"0000-0002-7146-9119","position":3,"is_corresponding":false},{"id":1162564,"name":"Arturo Andrade","orcid":"0000-0001-6585-2413","position":4,"is_corresponding":false},{"id":1191132,"name":"Célio José de Castro","orcid":"0000-0002-0063-4471","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T01:21:38.940853Z","pmid":"37693414","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}