{"doi":"10.1111/micc.12733","title":"Differential hyperpolarization to substance P and calcitonin gene‐related peptide in smooth muscle versus endothelium of mouse mesenteric artery","abstract":"Abstract Objective We sought to define how sensory neurotransmitters substance P and calcitonin gene‐related peptide (CGRP) affect membrane potential of vascular smooth muscle and endothelium. Methods Microelectrodes recorded membrane potential of smooth muscle from pressurized mouse mesenteric arteries (diameter, ~150 µm) and in endothelial tubes. Results Resting potential was similar (~ −45 mV) for each cell layer. Substance P hyperpolarized smooth muscle and endothelium ~ −15 mV; smooth muscle hyperpolarization was abolished by endothelial disruption or NO synthase inhibition. Blocking K Ca channels (apamin + charybdotoxin) attenuated hyperpolarization in both cell types. CGRP hyperpolarized endothelium and smooth muscle ~ −30 mV; smooth muscle hyperpolarization was independent of endothelium. Blocking K Ca channels prevented hyperpolarization to CGRP in endothelium but not smooth muscle. Inhibiting K ATP channels with glibenclamide or genetic deletion of K IR 6.1 attenuated hyperpolarization in smooth muscle but not endothelium. Pinacidil (K ATP channel agonist) hyperpolarized smooth muscle more than endothelium (~ −35 vs. ~ −20 mV). Conclusions Calcitonin gene‐related peptide elicits greater hyperpolarization than substance P. Substance P hyperpolarizes both cell layers through K Ca channels and involves endothelium‐derived NO in smooth muscle. Endothelial hyperpolarization to CGRP requires K Ca channels, while K ATP channels mediate hyperpolarization in smooth muscle. Differential K + channel activation in smooth muscle and endothelium through sensory neurotransmission may selectively tune mesenteric blood flow.","journal":"Microcirculation","year":2021,"id":197403,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":713156,"name":"Erika M. Boerman","orcid":"0000-0001-8103-3485","position":1,"is_corresponding":false},{"id":588940,"name":"Steven S. Segal","orcid":"0000-0001-5667-2154","position":2,"is_corresponding":false},{"id":532178,"name":"Charles E. Norton","orcid":"0000-0001-9442-4039","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T23:50:23.532351Z","pmid":"34633728","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":[]}