{"doi":"10.3389/fphys.2023.1242975","title":"Adenosine stimulates the basolateral 50 pS K+ channel in renal proximal tubule via adenosine-A1 receptor","abstract":"Background: The basolateral potassium channels play an important role in maintaining the membrane transport in the renal proximal tubules (PT) and adenosine receptors have been shown to regulate the trans-epithelial Na + absorption in the PT. The aim of the present study is to explore whether adenosine also regulates the basolateral K + channel of the PT and to determine the adenosine receptor type and the signaling pathway which mediates the effect of adenosine on the K + channel. Methods: We have used the single channel recording to examine the basolateral K + channel activity in the proximal tubules of the mouse kidney. All experiments were performed in cell-attached patches. Results: Single channel recording has detected a 50 pS inwardly-rectifying K + channel with high channel open probability and this 50 pS K + channel is a predominant type K + channel in the basolateral membrane of the mouse PT. Adding adenosine increased 50 pS K + channel activity in cell-attached patches, defined by NP o (a product of channel Numbers and Open Probability). The adenosine-induced stimulation of the 50 pS K + channel was absent in the PT pretreated with DPCPX, a selective inhibitor of adenosine A1 receptor. In contrast, adenosine was still able to stimulate the 50 pS K + channel in the PT pretreated with CP-66713, a selective adenosine A2 receptor antagonist. This suggests that the stimulatory effect of adenosine on the 50 pS K + channel of the PT was mediated by adenosine-A1 receptor. Moreover, the effect of adenosine on the 50 pS K + channel was blocked in the PT pretreated with U-73122 or Calphostin C, suggesting that adenosine-induced stimulation of the 50 pS K + channels of the PT was due to the activation of phospholipase C (PLC) and protein kinase C (PKC) pathway. In contrast, the inhibition of phospholipase A2 (PLA2) with AACOCF3 or inhibition of protein kinase A (PKA) with H8 failed to block the adenosine-induced stimulation of the 50 pS K + channel of the PT. Conclusion: We conclude that adenosine activates the 50 pS K + channels in the basolateral membrane of PT via adenosine-A1 receptor. Furthermore, the effect of adenosine on the 50 pS K + channel is mediated by PLC-PKC signaling pathway.","journal":"Frontiers in Physiology","year":2023,"id":377464,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"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":352540,"name":"Qi Sun","orcid":"0009-0001-3262-9802","position":1,"is_corresponding":false},{"id":1140851,"name":"Zheng Ding","orcid":"0000-0001-8201-1974","position":2,"is_corresponding":false},{"id":1141153,"name":"Wen-Sen Shi","orcid":null,"position":3,"is_corresponding":false},{"id":356411,"name":"Wen‐Hui Wang","orcid":"0000-0002-7503-9554","position":4,"is_corresponding":false},{"id":1141154,"name":"Chengbiao Zhang","orcid":null,"position":5,"is_corresponding":false},{"id":1140850,"name":"Hao Liu","orcid":"0009-0004-2137-0892","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T01:16:36.370283Z","pmid":"37700760","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":[]}