{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T14:52:20Z","timestamp":1773067940371,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T00:00:00Z","timestamp":1735516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01-DK104708"],"award-info":[{"award-number":["R01-DK104708"]}]},{"name":"National Institutes of Health","award":["2019\/32\/T\/NZ4\/00546"],"award-info":[{"award-number":["2019\/32\/T\/NZ4\/00546"]}]},{"name":"National Science Centre, Poland","award":["R01-DK104708"],"award-info":[{"award-number":["R01-DK104708"]}]},{"name":"National Science Centre, Poland","award":["2019\/32\/T\/NZ4\/00546"],"award-info":[{"award-number":["2019\/32\/T\/NZ4\/00546"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Podocytes express large-conductance Ca2+-activated K+ channels (BK channels) and at least two different pore-forming KCa1.1 subunit C-terminal splice variants, known as VEDEC and EMVYR, along with auxiliary \u03b2 and \u03b3 subunits. Podocyte KCa1.1 subunits interact directly with TRPC6 channels and BK channels become active in response to Ca2+ influx through TRPC6. Here, we confirmed that Ca2+ influx through TRPC channels is reduced following the blockade of BK channels by paxilline. The overall abundance of KCa1.1 subunits, as well as that of \u03b24 and \u03b33 subunits, were increased in glomeruli isolated from Sprague Dawley rats during chronic puromycin aminonucleoside (PAN) nephrosis. Exposing cultured mouse podocytes for 24 h to recombinant TNF\u03b1, a circulating factor implicated in pediatric nephrotic syndromes, did not affect the total abundance of KCa1.1, but did evoke significant increases in both \u03b24 and \u03b33. However, TNF\u03b1 evoked a marked increase in the surface abundance of KCa1.1 subunits, similar to that of its previously reported effects on TRPC6 channels. The effect of TNF\u03b1 on the surface expression of KCa1.1 was eliminated following siRNA knockdown of the \u03b24 subunits, suggesting a role for this subunit in KCa1.1 trafficking to the cell surface. By contrast, treating podocytes with suPAR did not affect the total or surface expression of KCa1.1. The coordinated activation of KCa1.1 channels may promote Ca2+ influx through TRPC channels during normal and abnormal podocyte function by maintaining a membrane potential that allows for the efficient permeation of divalent cations through TRPC pores.<\/jats:p>","DOI":"10.3390\/cells14010022","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T07:51:57Z","timestamp":1735631517000},"page":"22","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dysregulation of Podocyte BK Channels and Nephrosis: Effects of Circulating Factors and Auxiliary \u03b24 Subunits"],"prefix":"10.3390","volume":"14","author":[{"given":"Eun Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7691-8243","authenticated-orcid":false,"given":"Patrycja","family":"Rachubik","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA"},{"name":"Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart E.","family":"Dryer","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA"},{"name":"Department of Biomedical Sciences, Tilman J. Fertitta Family College of Medicine, University of Houston, Houston, TX 77204, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.bbadis.2019.04.001","article-title":"TRPC channels: Regulation, dysregulation and contributions to chronic kidney disease","volume":"1865","author":"Dryer","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. 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