{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:13:02Z","timestamp":1791259982299,"version":"4.1.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,1,23]]},"abstract":"\n Background<\/jats:title>\n \n Attenuated cardiac vagal activity is associated with ventricular arrhythmogenesis and related mortality in patients with chronic heart failure. Our recent study has shown that expression of N\u2010type Ca\n 2+<\/jats:sup>\n channel \u03b1\u2010subunits (Ca\n v<\/jats:sub>\n 2.2\u2010\u03b1) and N\u2010type Ca\n 2+<\/jats:sup>\n currents are reduced in intracardiac ganglion neurons from rats with chronic heart failure. Rat intracardiac ganglia are divided into the atrioventricular ganglion (\n AVG<\/jats:styled-content>\n ) and sinoatrial ganglion. Ventricular myocardium receives projection of neuronal terminals only from the\n AVG<\/jats:styled-content>\n . In this study we tested whether a decrease in N\u2010type Ca\n 2+<\/jats:sup>\n channels in\n AVG<\/jats:styled-content>\n neurons contributes to ventricular arrhythmogenesis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Lentiviral Ca\n v<\/jats:sub>\n 2.2\u2010\u03b1 sh\n RNA<\/jats:styled-content>\n (2\u00a0\u03bcL, 2\u00d710\n 7<\/jats:sup>\n \u00a0pfu\/mL) or scrambled sh\n RNA<\/jats:styled-content>\n was in\u00a0vivo transfected into rat\n AVG<\/jats:styled-content>\n neurons. Nontransfected sham rats served as controls. Using real\u2010time single\u2010cell polymerase chain reaction and reverse\u2010phase protein array, we found that in\u00a0vivo transfection of Ca\n v<\/jats:sub>\n 2.2\u2010\u03b1 sh\n RNA<\/jats:styled-content>\n decreased expression of Ca\n v<\/jats:sub>\n 2.2\u2010\u03b1\n mRNA<\/jats:styled-content>\n and protein in rat\n AVG<\/jats:styled-content>\n neurons. Whole\u2010cell patch\u2010clamp data showed that Ca\n v<\/jats:sub>\n 2.2\u2010\u03b1 sh\n RNA<\/jats:styled-content>\n reduced N\u2010type Ca\n 2+<\/jats:sup>\n currents and cell excitability in\n AVG<\/jats:styled-content>\n neurons. The data from telemetry electrocardiographic recording demonstrated that 83% (5 out of 6) of conscious rats with Ca\n v<\/jats:sub>\n 2.2\u2010\u03b1 sh\n RNA<\/jats:styled-content>\n transfection had premature ventricular contractions (\n P<\/jats:italic>\n <0.05 versus 0% of nontransfected sham rats or scrambled sh\n RNA<\/jats:styled-content>\n \u2010transfected rats). Additionally, an index of susceptibility to ventricular arrhythmias, inducibility of ventricular arrhythmias evoked by programmed electrical stimulation, was higher in rats with Ca\n v<\/jats:sub>\n 2.2\u2010\u03b1 sh\n RNA<\/jats:styled-content>\n transfection compared with nontransfected sham rats and scrambled sh\n RNA<\/jats:styled-content>\n \u2010transfected rats.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n A decrease in N\u2010type Ca\n 2+<\/jats:sup>\n channels in\n AVG<\/jats:styled-content>\n neurons attenuates vagal control of ventricular myocardium, thereby initiating ventricular arrhythmias.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.007457","type":"journal-article","created":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T20:11:02Z","timestamp":1516047062000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Reduced N\u2010Type Ca\n 2+<\/sup>\n Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis"],"prefix":"10.1161","volume":"7","author":[{"given":"Dongze","family":"Zhang","sequence":"first","affiliation":[{"name":"University of Nebraska Medical Center","place":["Omaha"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyin","family":"Tu","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center","place":["Omaha"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Cao","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center","place":["Omaha"]},{"name":"Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zheng","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center","place":["Omaha"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Muelleman","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center","place":["Omaha"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Wadman","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center","place":["Omaha"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Long","family":"Li","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center","place":["Omaha"]},{"name":"University of Nebraska Medical Center","place":["Omaha"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1016\/j.jacc.2005.09.016","article-title":"Mode of death in advanced heart failure: the Comparison of Medical, Pacing, and Defibrillation Therapies in Heart Failure (COMPANION) trial","volume":"46","author":"Carson P","year":"2005","unstructured":"Carson P, Anand I, O'Connor C, Jaski B, Steinberg J, Lwin A, Lindenfeld J, Ghali J, Barnet JH, Feldman AM, Bristow MR. 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