{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T06:50:45Z","timestamp":1776408645551,"version":"3.51.2"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,12,2]]},"abstract":"\n Background<\/jats:title>\n \n Guanylyl cyclase, a heme\u2010containing \u03b11\u03b21 heterodimer (\n GC<\/jats:styled-content>\n 1), produces\n cGMP<\/jats:styled-content>\n in response to Nitric oxide (\n NO<\/jats:styled-content>\n ) stimulation. The\n NO<\/jats:styled-content>\n \u2010\n GC1<\/jats:styled-content>\n \u2010\n cGMP<\/jats:styled-content>\n pathway negatively regulates cardiomyocyte contractility and protects against cardiac hypertrophy\u2013related remodeling. We recently reported that the \u03b21 subunit of\n GC<\/jats:styled-content>\n 1 is detected at the intercalated disc with connexin 43 (Cx43). Cx43 forms gap junctions (\n GJs<\/jats:styled-content>\n ) at the intercalated disc that are responsible for electrical propagation. We sought to determine whether there is a functional association between\n GC<\/jats:styled-content>\n 1 and Cx43 and its role in cardiac homeostasis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n GC<\/jats:styled-content>\n 1 and Cx43 immunostaining at the intercalated disc and coimmunoprecipitation from membrane fraction indicate that\n GC<\/jats:styled-content>\n 1 and Cx43 are associated. Mice lacking the \u03b1 subunit of\n GC<\/jats:styled-content>\n 1 (\n GC<\/jats:styled-content>\n \u03b11 knockout mice) displayed a significant decrease in\n GJ<\/jats:styled-content>\n function (dye\u2010spread assay) and Cx43 membrane lateralization. In a cardiac\u2010hypertrophic model, angiotensin\n II<\/jats:styled-content>\n treatment disrupted the GC1\u2010Cx43 association and induced significant Cx43 membrane lateralization, which was exacerbated in\n GC<\/jats:styled-content>\n \u03b11 knockout mice. Cx43 lateralization correlated with decreased Cx43\u2010containing\n GJs<\/jats:styled-content>\n at the intercalated disc, predictors of electrical dysfunction. Accordingly, an ECG revealed that angiotensin\n II<\/jats:styled-content>\n \u2013treated\n GC<\/jats:styled-content>\n \u03b11 knockout mice had impaired ventricular electrical propagation. The phosphorylation level of Cx43 at serine 365, a protein\u2010kinase A upregulated site involved in trafficking\/assembly of\n GJs<\/jats:styled-content>\n , was decreased in these models.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n GC<\/jats:styled-content>\n 1 modulates ventricular Cx43 location, hence\n GJ<\/jats:styled-content>\n function, and partially protects from electrical dysfunction in an angiotensin\n II<\/jats:styled-content>\n hypertrophy model. Disruption of the\n NO<\/jats:styled-content>\n \u2010\n cGMP<\/jats:styled-content>\n pathway is associated with cardiac electrical disturbance and abnormal Cx43 phosphorylation. This previously unknown\n NO<\/jats:styled-content>\n \/Cx43 signaling could be a protective mechanism against stress\u2010induced arrhythmia.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.006397","type":"journal-article","created":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T01:12:11Z","timestamp":1513905131000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Newly Identified NO\u2010Sensor Guanylyl Cyclase\/Connexin 43 Association Is Involved in Cardiac Electrical Function"],"prefix":"10.1161","volume":"6","author":[{"given":"Pierre\u2010Antoine","family":"Crassous","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School\u2013Rutgers, Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School\u2013Rutgers, Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Can","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School\u2013Rutgers, Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Gordan","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine, New Jersey Medical School\u2013Rutgers, Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Brouckaert","sequence":"additional","affiliation":[{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul D.","family":"Lampe","sequence":"additional","affiliation":[{"name":"Human Biology Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lai\u2010Hua","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Medicine, New Jersey Medical School\u2013Rutgers, Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annie","family":"Beuve","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School\u2013Rutgers, Newark, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1001360107"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01273.2010"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1414364111"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.05.021"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb775"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.111.259242"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.09.011"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt095"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00038.2012"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-007-9035-y"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.01.049"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000246118.98832.04"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010716-104756"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.02.009"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00138.2012"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01400.2006"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.07.048"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn068"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvm083"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.274.3.H747"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.06.002"},{"key":"e_1_3_4_23_2","first-page":"67","article-title":"Remodelling of cardiac gap junction connexin 43 and arrhythmogenesis","volume":"12","author":"Mayama T","year":"2007","unstructured":"Mayama T, Matsumura K, Lin H, Ogawa K, Imanaga I. 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