{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T13:36:38Z","timestamp":1778938598786,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,2,25]],"date-time":"2016-02-25T00:00:00Z","timestamp":1456358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>The goal of this study was to evaluate sex differences and the role of the potassium channel \u03b21 (Kv\u03b21) subunit in the heart.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>Genetic ablation of Kv\u03b21.1 in females led to cardiac hypertrophy characterized by increased heart size, prolonged monophasic action potentials, elevated blood pressure and increased myosin heavy chain \u03b1 (MHC\u03b1) expression. In contrast, male mice showed only electrical changes. Kv\u03b21.1 binds the MHC\u03b1 isoform at the protein level, and small interfering RNA targeted knockdown of Kv\u03b21.1 upregulated MHC\u03b1.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Cardiovascular disease is the leading cause of death and debility in women in the USA, and cardiac arrhythmias are a major concern. Voltage\u2010gated potassium (Kv) channels along with the binding partners; Kv\u03b2 subunits are major regulators of the action potential (AP) shape and duration (APD). The regulation of Kv channels by the Kv\u03b21 subunit is unknown in female hearts. In the present study, we hypothesized that the Kv\u03b21 subunit is an important regulator of female cardiac physiology. To test this hypothesis, we ablated (knocked out; KO) the KCNAB1 isoform 1 (Kv\u03b21.1) subunit in mice and evaluated cardiac function and electrical activity by using ECG, monophasic action potential recordings and echocardiography. Our results showed that the female Kv\u03b21.1 KO mice developed cardiac hypertrophy, and the hearts were structurally different, with enlargement and increased area. The electrical derangements caused by Kv\u03b21.1 KO in female mice included long QTc and QRS intervals along with increased APD (APD20\u201390% repolarization). The male Kv\u03b21.1 KO mice did not develop cardiac hypertrophy, but they showed long QTc and prolonged APD. Molecular analysis showed that several genes that support cardiac hypertrophy were significantly altered in Kv\u03b21.1 KO female hearts. In particular, myosin heavy chain\u00a0\u03b1 expression was significantly elevated in Kv\u03b21.1 KO mouse heart. Using a small interfering RNA strategy, we identified that knockdown of Kv\u03b21 increases myosin heavy chain\u00a0\u03b1 expression in H9C2 cells. Collectively, changes in molecular and cell signalling pathways clearly point towards a distinct electrical and structural remodelling consistent with cardiac hypertrophy in the Kv\u03b21.1 KO female mice.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep085405","type":"journal-article","created":{"date-parts":[[2016,1,6]],"date-time":"2016-01-06T10:08:06Z","timestamp":1452074886000},"page":"494-508","source":"Crossref","is-referenced-by-count":22,"title":["Deletion of Kv\u03b21.1 subunit leads to electrical and haemodynamic changes causing cardiac hypertrophy in female murine hearts"],"prefix":"10.1113","volume":"101","author":[{"given":"Jared","family":"Tur","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy  Tampa FL USA"},{"name":"Department of Molecular Medicine, Morsani College of Medicine University of South Florida  Tampa FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalyan C.","family":"Chapalamadugu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy  Tampa FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Padawer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy  Tampa FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachin L.","family":"Badole","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy  Tampa FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"II","given":"Peter J.","family":"Kilfoil","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Center University of Louisville  Louisville KY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aruni","family":"Bhatnagar","sequence":"additional","affiliation":[{"name":"Diabetes and Obesity Center University of Louisville  Louisville KY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srinivas M.","family":"Tipparaju","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy  Tampa FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,2,25]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000156890.25876.63"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000167822"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1994.03510350050036"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.10.2641"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2014.10.019"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1753-6561-8-S1-S109"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2015.04.802"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2015.105"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.328278"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.845792"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00187-5"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/jwh.1998.7.547"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.07.013"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1995.00430050045005"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-014-0965-5"},{"key":"e_1_2_5_17_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1101\/lm.5.4.257","article-title":"Reduced K+ channel inactivation, spike broadening, and after\u2010hyperpolarization in Kv\u03b21.1\u2010deficient mice with impaired learning","volume":"5","author":"Giese KP","year":"1998","journal-title":"Learn Mem"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e318282ab8f"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/CRD.0b013e318259294b"},{"key":"e_1_2_5_20_1","first-page":"365","article-title":"GATA\u20104 promotes the differentiation of P19 cells into cardiac myocytes","volume":"26","author":"Hu DL","year":"2010","journal-title":"Int J Mol Med"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.10.2535"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-013-0056-x"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.113.000190"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.11.004"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1993.03510210076031"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.274.3.H747"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.7.4947"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.10.021"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2014.02.003"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2012.01.009"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306642"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl143"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060545"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00474.2012"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.17.2207"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00020.2009"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/369289a0"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00022.2013"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608874200"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2014.03.032"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-012-1093-z"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.05.102"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.22.9829-9844.2005"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2015.01.017"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-0736(97)80038-6"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.10.086"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FEP085405","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP085405","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T17:43:24Z","timestamp":1696009404000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP085405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,25]]},"references-count":45,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1113\/EP085405"],"URL":"https:\/\/doi.org\/10.1113\/ep085405","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,25]]}}}