Heart Rate and Extracellular Sodium and Potassium Modulation of Gap Junction Mediated Conduction in Guinea Pigs

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dc.contributor.authorEntz, Michael, IIen
dc.contributor.authorGeorge, Sharon A.en
dc.contributor.authorZeitz, Michael J.en
dc.contributor.authorRaisch, Tristan B.en
dc.contributor.authorSmyth, James W.en
dc.contributor.authorPoelzing, Stevenen
dc.contributor.departmentBiological Sciencesen
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.date.accessioned2017-02-03T15:09:32Zen
dc.date.available2017-02-03T15:09:32Zen
dc.date.issued2016-02-02en
dc.description.abstractBackground: Recent studies suggested that cardiac conduction in murine hearts with narrow perinexi and 50% reduced connexin43 (Cx43) expression is more sensitive to relatively physiological changes of extracellular potassium ([K+](o)) and sodium ([Na+](o)). Purpose: Determine whether similar [K+](o) and [Na+](o) changes alter conduction velocity (CV) sensitivity to pharmacologic gap junction (GJ) uncoupling in guinea pigs. Methods: [K+](o) and [Na+](o) were varied in Langendorff perfused guinea pig ventricles (Solution A: [K+](o) = 4.56 and [N+](o) = 153.3 mM. Solution B: [K+](o) = 6.95 and [Na+](o) = 145.5 mM). Gap junctions were inhibited with carbenoxolone (CBX) (15 and 30 mu M). Epicardial CV was quantified by optical mapping. Perinexal width was measured with transmission electron microscopy. Total and phosphorylated Cx43 were evaluated by western blotting. Results: Solution composition did not alter CV under control conditions or with 15 mu M CBX. Decreasing the basic cycle length (BCL) of pacing from 300 to 160 ms decreased CV uniformly with both solutions. At 30 mu M CBX, a change in solution did not alter CV either longitudinally or transversely at BCL = 300 ms. However, reducing BCL to 160 ms caused CV to decrease more in hearts perfused with Solution B than A. Solution composition did not alter perinexal width, nor did it change total or phosphorylated serine 368 Cx43 expression. These data suggest that the solution dependent CV changes were independent of altered perinexal width or GJ coupling. Action potential duration was always shorter in hearts perfused with Solution B than A. independent of pacing rate and/or CBX concentration. Conclusions: Increased heart rate and GJ uncoupling can unmask small CV differences caused by changing [K+](o) and [Na+](o). These data suggest that modulating extracellular ionic composition may be a novel anti-arrhythmic target in diseases with abnormal GJ coupling, particularly when heart rate cannot be controlled.en
dc.description.versionPublished versionen
dc.format.extent10 pagesen
dc.identifier.doihttps://doi.org/10.3389/fphys.2016.00016en
dc.identifier.issn1664-042Xen
dc.identifier.urihttp://hdl.handle.net/10919/74920en
dc.identifier.volume7en
dc.language.isoenen
dc.publisherFrontiersen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000369058400001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectPhysiologyen
dc.subjectelectrophysiologyen
dc.subjectcardiac conductionen
dc.subjectephaptic couplingen
dc.subjectgap junctionen
dc.subjectALTERED CONNEXIN43 EXPRESSIONen
dc.subjectCARDIAC CONDUCTIONen
dc.subjectIMPULSE PROPAGATIONen
dc.subjectPURKINJE-FIBERSen
dc.subjectMECHANISMSen
dc.subjectMODELen
dc.subjectISCHEMIAen
dc.subjectVELOCITYen
dc.subjectCELLSen
dc.subjectHEMICHANNELSen
dc.titleHeart Rate and Extracellular Sodium and Potassium Modulation of Gap Junction Mediated Conduction in Guinea Pigsen
dc.title.serialFrontiers in Physiologyen
dc.typeArticle - Refereeden
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Virginia Tech Carilion Research Instituteen

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