Chien-Jung Chang1, Chen-Chuan Cheng2, Yao-Chang Chen3, Yu-Hsun Kao4, Shih-Ann Chen5, Yi-Jen Chen6. 1. Division of Cardiology, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan. 2. Division of Cardiology, Chi-Mei Medical Center, Tainan, Taiwan; Chung Shan Medical University, Department of Internal Medicine, Taichung, Taiwan. 3. Department of Biomedical Engineering and Institute of Physiology, National Defense Medical Center, Taipei, Taiwan. 4. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 5. National Yang-Ming University, School of Medicine, Taipei, Taiwan; Division of Cardiology and Cardiovascular Research Center, Taipei Veterans General Hospital, Taipei, Taiwan. 6. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: a9900112@ms15.hinet.net.
Abstract
BACKGROUND: Gap junction (GJ) dysfunctions predispose cardiac tissues to various arrhythmias. Sinoatrial node (SAN) and pulmonary veins (PVs) are closely related atrial dysrhythmia. This study evaluated whether GJ modifications modulate SAN and PVs electrical activities. METHODS: Conventional microelectrodes were used to record action potentials in isolated rabbit SAN, PVs, and connected PV-SAN tissue preparations before and after heptanol (GJ inhibitor) and PQ1 (GJ enhancer) administration with and without isoproterenol. A whole-cell patch clamp was used to record the electrical activities before and after heptanol in single SAN and PV cardiomyocytes. RESULTS: Heptanol (1, 3, and 10μM) reduced the spontaneous beating rates of isolated SAN preparations but not PVs. Heptanol (10μM) decelerated the SAN leading rhythm in the PV-SAN preparations and induced PV burst firings without (3 of 6, 50%) and with (6 of 6, 100%) isoproterenol (1μM). Heptanol (10μM) also reduced the spontaneous beating rates in single SAN cardiomyocyte, but not PV cardiomyocyte, with a decreased pacemaker current. PQ1 (50 and 500nM) treatment did not change the spontaneous beating rates in isolated SAN and PV preparations. In the connected PV-SAN preparations, PQ1 (500nM) did not induce any PV firing even having additional isoproterenol treatment (1μM). Moreover, PQ1 (500nM) prevented heptanol-induced electrical changes in SAN and PVs preparations. CONCLUSION: GJ dysfunction modulates SAN and PV electrical activity, which may contribute to atrial arrhythmogenesis. GJ enhancer has a therapeutic potential in SAN dysfunction and atrial arrhythmogenesis.
BACKGROUND: Gap junction (GJ) dysfunctions predispose cardiac tissues to various arrhythmias. Sinoatrial node (SAN) and pulmonary veins (PVs) are closely related atrial dysrhythmia. This study evaluated whether GJ modifications modulate SAN and PVs electrical activities. METHODS: Conventional microelectrodes were used to record action potentials in isolated rabbit SAN, PVs, and connected PV-SAN tissue preparations before and after heptanol (GJ inhibitor) and PQ1 (GJ enhancer) administration with and without isoproterenol. A whole-cell patch clamp was used to record the electrical activities before and after heptanol in single SAN and PV cardiomyocytes. RESULTS:Heptanol (1, 3, and 10μM) reduced the spontaneous beating rates of isolated SAN preparations but not PVs. Heptanol (10μM) decelerated the SAN leading rhythm in the PV-SAN preparations and induced PV burst firings without (3 of 6, 50%) and with (6 of 6, 100%) isoproterenol (1μM). Heptanol (10μM) also reduced the spontaneous beating rates in single SAN cardiomyocyte, but not PV cardiomyocyte, with a decreased pacemaker current. PQ1 (50 and 500nM) treatment did not change the spontaneous beating rates in isolated SAN and PV preparations. In the connected PV-SAN preparations, PQ1 (500nM) did not induce any PV firing even having additional isoproterenol treatment (1μM). Moreover, PQ1 (500nM) prevented heptanol-induced electrical changes in SAN and PVs preparations. CONCLUSION: GJ dysfunction modulates SAN and PV electrical activity, which may contribute to atrial arrhythmogenesis. GJ enhancer has a therapeutic potential in SAN dysfunction and atrial arrhythmogenesis.
Authors: Gary Tse; Tong Liu; Guangping Li; Wendy Keung; Jie Ming Yeo; Yin Wah Fiona Chan; Bryan P Yan; Yat Sun Chan; Sunny Hei Wong; Ronald A Li; Jichao Zhao; William K K Wu; Wing Tak Wong Journal: Oncotarget Date: 2017-07-28