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However, their electrophysiological properties in humans are poorly defined. Here, we characterized ionic currents and their modulation in primary human CCs obtained from patients undergoing in\u00a0vitro fertilization. Whole cell patch\u2010clamp recordings identified three electrophysiological sub\u2010populations: CC\u2010type 1, expressing voltage\u2010dependent K\n                    <jats:sup>+<\/jats:sup>\n                    currents supported mainly by potassium voltage\u2010gated channel subfamily A member 5 (K\n                    <jats:sub>V<\/jats:sub>\n                    1.5, KCNA5); CC\u2010type 2, predominantly showing a barium\u2010sensitive cationic current attributable to transient receptor potential cation channel subfamily M member 5 (TRPM5); and CC\u2010type 3, displaying mainly a noisy and voltage\u2010dependent K\n                    <jats:sup>+<\/jats:sup>\n                    current typical of potassium calcium\u2010activated channel subfamily M alpha 1 (BK\n                    <jats:sub>Ca<\/jats:sub>\n                    , KCNMA1). Pharmacological experiments, immunocytochemistry and rt\u2010PCR confirmed the molecular expression of KCNA5, TRPM5 and KCNMA1. Mild extracellular acidification (pH\u2009=\u20096.2) rapidly and reversibly blocked TRPM5\u2010like current, both inward and outward. Furthermore, 100\u2009\u03bcM ATP induced metabotropic responses, evoking coupled intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release and activating TRPM5\u2010mediated currents, as demonstrated by experiments with patch\u2010clamp and FURA\u20102 calcium imaging. These findings reveal that human CCs integrate extracellular acidity and purinergic signals via distinct ion channels, suggesting a role as electrochemical sensors of the follicular microenvironment.\n                  <\/jats:p>","DOI":"10.14814\/phy2.70729","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:51:26Z","timestamp":1769604686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular acidity and\n                    <scp>ATP<\/scp>\n                    modulate ion currents in human cumulus cells indicating possible roles as metabolic sensors of the follicular microenvironment"],"prefix":"10.14814","volume":"14","author":[{"given":"Andrea","family":"Biagini","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery University of Perugia  Perugia Italy"},{"name":"Department of Chemistry, Biology and Biotechnologies University of Perugia  Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosaria","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnologies University of Perugia  Perugia Italy"},{"name":"Interdepartmental Laboratory of Reproductive Physiopathology University of Perugia  Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Corbucci","sequence":"additional","affiliation":[{"name":"Centre of Assisted Reproductive Technologies S. Maria della Misericordia Hospital  Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Mariani","sequence":"additional","affiliation":[{"name":"Centre of Assisted Reproductive Technologies S. Maria della Misericordia Hospital  Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Favilli","sequence":"additional","affiliation":[{"name":"Interdepartmental Laboratory of Reproductive Physiopathology University of Perugia  Perugia Italy"},{"name":"Centre of Assisted Reproductive Technologies S. Maria della Misericordia Hospital  Perugia Italy"},{"name":"Section of Obstetrics and Gynecology, Department of Medicine and Surgery University of Perugia  Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandro","family":"Gerli","sequence":"additional","affiliation":[{"name":"Interdepartmental Laboratory of Reproductive Physiopathology University of Perugia  Perugia Italy"},{"name":"Centre of Assisted Reproductive Technologies S. Maria della Misericordia Hospital  Perugia Italy"},{"name":"Section of Obstetrics and Gynecology, Department of Medicine and Surgery University of Perugia  Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9570-4195","authenticated-orcid":false,"given":"Bernard","family":"Fioretti","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnologies University of Perugia  Perugia Italy"},{"name":"Interdepartmental Laboratory of Reproductive Physiopathology University of Perugia  Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.4103\/2277-9175.170675","article-title":"Isolation of granulosa cells from follicular fluid; applications in biomedical and molecular biology experiments","volume":"4","author":"Aghadavod E.","year":"2015","journal-title":"Advanced Biomedical Research"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1530\/rep.0.1210647"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.003889"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.20921"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod66.3.836"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23020886"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22523"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.159384"},{"key":"e_1_2_10_10_1","first-page":"117","article-title":"Ovarian follicular and luteal physiology","volume":"22","author":"Channing C. 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