A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity.
<h4>Background</h4>The left atrial posterior wall (LAPW) is potentially an important area for the development and maintenance of atrial fibrillation. We assessed whether there are regional electrical differences throughout the murine left atrial myocardium that could underlie regional di...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0154077 |
| _version_ | 1819025885944086528 |
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| author | Andrew P Holmes Ting Y Yu Samantha Tull Fahima Syeda Stefan M Kuhlmann Sian-Marie O'Brien Pushpa Patel Keith L Brain Davor Pavlovic Nigel A Brown Larissa Fabritz Paulus Kirchhof |
| author_facet | Andrew P Holmes Ting Y Yu Samantha Tull Fahima Syeda Stefan M Kuhlmann Sian-Marie O'Brien Pushpa Patel Keith L Brain Davor Pavlovic Nigel A Brown Larissa Fabritz Paulus Kirchhof |
| author_sort | Andrew P Holmes |
| collection | DOAJ |
| description | <h4>Background</h4>The left atrial posterior wall (LAPW) is potentially an important area for the development and maintenance of atrial fibrillation. We assessed whether there are regional electrical differences throughout the murine left atrial myocardium that could underlie regional differences in arrhythmia susceptibility.<h4>Methods</h4>We used high-resolution optical mapping and sharp microelectrode recordings to quantify regional differences in electrical activation and repolarisation within the intact, superfused murine left atrium and quantified regional ion channel mRNA expression by Taqman Low Density Array. We also performed selected cellular electrophysiology experiments to validate regional differences in ion channel function.<h4>Results</h4>Spontaneous ectopic activity was observed during sustained 1Hz pacing in 10/19 intact LA and this was abolished following resection of LAPW (0/19 resected LA, P<0.001). The source of the ectopic activity was the LAPW myocardium, distinct from the pulmonary vein sleeve and LAA, determined by optical mapping. Overall, LAPW action potentials (APs) were ca. 40% longer than the LAA and this region displayed more APD heterogeneity. mRNA expression of Kcna4, Kcnj3 and Kcnj5 was lower in the LAPW myocardium than in the LAA. Cardiomyocytes isolated from the LAPW had decreased Ito and a reduced IKACh current density at both positive and negative test potentials.<h4>Conclusions</h4>The murine LAPW myocardium has a different electrical phenotype and ion channel mRNA expression profile compared with other regions of the LA, and this is associated with increased ectopic activity. If similar regional electrical differences are present in the human LA, then the LAPW may be a potential future target for treatment of atrial fibrillation. |
| first_indexed | 2024-12-21T05:17:48Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T05:17:48Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fb2c0df40e77457cb0987ba54a3db1b92022-12-21T19:14:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01115e015407710.1371/journal.pone.0154077A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity.Andrew P HolmesTing Y YuSamantha TullFahima SyedaStefan M KuhlmannSian-Marie O'BrienPushpa PatelKeith L BrainDavor PavlovicNigel A BrownLarissa FabritzPaulus Kirchhof<h4>Background</h4>The left atrial posterior wall (LAPW) is potentially an important area for the development and maintenance of atrial fibrillation. We assessed whether there are regional electrical differences throughout the murine left atrial myocardium that could underlie regional differences in arrhythmia susceptibility.<h4>Methods</h4>We used high-resolution optical mapping and sharp microelectrode recordings to quantify regional differences in electrical activation and repolarisation within the intact, superfused murine left atrium and quantified regional ion channel mRNA expression by Taqman Low Density Array. We also performed selected cellular electrophysiology experiments to validate regional differences in ion channel function.<h4>Results</h4>Spontaneous ectopic activity was observed during sustained 1Hz pacing in 10/19 intact LA and this was abolished following resection of LAPW (0/19 resected LA, P<0.001). The source of the ectopic activity was the LAPW myocardium, distinct from the pulmonary vein sleeve and LAA, determined by optical mapping. Overall, LAPW action potentials (APs) were ca. 40% longer than the LAA and this region displayed more APD heterogeneity. mRNA expression of Kcna4, Kcnj3 and Kcnj5 was lower in the LAPW myocardium than in the LAA. Cardiomyocytes isolated from the LAPW had decreased Ito and a reduced IKACh current density at both positive and negative test potentials.<h4>Conclusions</h4>The murine LAPW myocardium has a different electrical phenotype and ion channel mRNA expression profile compared with other regions of the LA, and this is associated with increased ectopic activity. If similar regional electrical differences are present in the human LA, then the LAPW may be a potential future target for treatment of atrial fibrillation.https://doi.org/10.1371/journal.pone.0154077 |
| spellingShingle | Andrew P Holmes Ting Y Yu Samantha Tull Fahima Syeda Stefan M Kuhlmann Sian-Marie O'Brien Pushpa Patel Keith L Brain Davor Pavlovic Nigel A Brown Larissa Fabritz Paulus Kirchhof A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity. PLoS ONE |
| title | A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity. |
| title_full | A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity. |
| title_fullStr | A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity. |
| title_full_unstemmed | A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity. |
| title_short | A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity. |
| title_sort | regional reduction in ito and ikach in the murine posterior left atrial myocardium is associated with action potential prolongation and increased ectopic activity |
| url | https://doi.org/10.1371/journal.pone.0154077 |
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