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The conduction velocity-potassium relationship in the heart is modulated by sodium and calcium

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dc.contributor.authorKing, D. Ryanen
dc.contributor.authorEntz, Michael, IIen
dc.contributor.authorBlair, Grace A.en
dc.contributor.authorCrandell, Ianen
dc.contributor.authorHanlon, Alexandra L.en
dc.contributor.authorLin, Joyceen
dc.contributor.authorHoeker, Gregory S.en
dc.contributor.authorPoelzing, Stevenen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.contributor.departmentVirginia Tech Carilion School of Medicineen
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.contributor.departmentCenter for Biostatistics and Health Data Scienceen
dc.date.accessioned2021-04-28T14:49:35Zen
dc.date.available2021-04-28T14:49:35Zen
dc.date.issued2021-03en
dc.description.abstractThe relationship between cardiac conduction velocity (CV) and extracellular potassium (K+) is biphasic, with modest hyperkalemia increasing CV and severe hyperkalemia slowing CV. Recent studies from our group suggest that elevating extracellular sodium (Na+) and calcium (Ca2+) can enhance CV by an extracellular pathway parallel to gap junctional coupling (GJC) called ephaptic coupling that can occur in the gap junction adjacent perinexus. However, it remains unknown whether these same interventions modulate CV as a function of K+. We hypothesize that Na+, Ca2+, and GJC can attenuate conduction slowing consequent to severe hyperkalemia. Elevating Ca2+ from 1.25 to 2.00 mM significantly narrowed perinexal width measured by transmission electron microscopy. Optically mapped, Langendorff-perfused guinea pig hearts perfused with increasing K+ revealed the expected biphasic CV-K+ relationship during perfusion with different Na+ and Ca2+ concentrations. Neither elevating Na+ nor Ca2+ alone consistently modulated the positive slope of CV-K+ or conduction slowing at 10-mM K+; however, combined Na+ and Ca2+ elevation significantly mitigated conduction slowing at 10-mM K+. Pharmacologic GJC inhibition with 30-mu M carbenoxolone slowed CV without changing the shape of CV-K+ curves. A computational model of CV predicted that elevating Na+ and narrowing clefts between myocytes, as occur with perinexal narrowing, reduces the positive and negative slopes of the CV-K+ relationship but do not support a primary role of GJC or sodium channel conductance. These data demonstrate that combinatorial effects of Na+ and Ca2+ differentially modulate conduction during hyperkalemia, and enhancing determinants of ephaptic coupling may attenuate conduction changes in a variety of physiologic conditions.en
dc.description.notesThis study was supported by National Institutes of Health F31-HL147438 awarded to DRK, National Institutes of Health R01-HL141855, R01-HL138003, and R01-HL102298 awarded to SP, and National Institutes of Health UL1TR003015 awarded to ALF.en
dc.description.sponsorshipNational Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [UL1TR003015, F31-HL147438, R01-HL141855, R01-HL138003, R01-HL102298]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1007/s00424-021-02537-yen
dc.identifier.eissn1432-2013en
dc.identifier.issn0031-6768en
dc.identifier.issue3en
dc.identifier.pmid33660028en
dc.identifier.urihttp://hdl.handle.net/10919/103158en
dc.identifier.volume473en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectHyperkalemiaen
dc.subjectSodiumen
dc.subjectCalciumen
dc.subjectCardiac Electrophysiologyen
dc.subjectLangendorffen
dc.titleThe conduction velocity-potassium relationship in the heart is modulated by sodium and calciumen
dc.title.serialPflugers Archiv-European Journal of Physiologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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