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SHR Neuro Krebs Kardio Lipid

Hammer, KP; Ljubojevic, S; Ripplinger, CM; Pieske, BM; Bers, DM.
Cardiac myocyte alternans in intact heart: Influence of cell-cell coupling and β-adrenergic stimulation.
J Mol Cell Cardiol. 2015; 84(2):1-9 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Holzer Senka
Pieske Burkert Mathias

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Number of Figures: 6
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Cardiac alternans are proarrhythmic and mechanistically link cardiac mechanical dysfunction and sudden cardiac death. Beat-to-beat alternans occur when beats with large Ca(2+) transients and long action potential duration (APD) alternate with the converse. APD alternans are typically driven by Ca(2+) alternans and sarcoplasmic reticulum (SR) Ca(2+) release alternans. But the effect of intercellular communication via gap junctions (GJ) on alternans in the intact heart remains unknown. We assessed the effects of cell-to-cell coupling on local alternans in intact Langendorff-perfused mouse hearts, measuring single myocyte [Ca(2+)] alternans synchronization among neighboring cells, and effects of β-adrenergic receptor (β-AR) activation and reduced GJ coupling. Mouse hearts (C57BL/6) were retrogradely perfused and loaded with Fluo8-AM to record cardiac myocyte [Ca(2+)] in situ with confocal microscopy. Single cell resolution allowed analysis of alternans within the intact organ during alternans induction. Carbenoxolone (25 μM), a GJ inhibitor, significantly increased the occurrence and amplitude of alternans in single cells within the intact heart. Alternans were concordant between neighboring cells throughout the field of view, except transiently during onset. β-AR stimulation only reduced Ca(2+) alternans in tissue that had reduced GJ coupling, matching effects seen in isolated myocytes. Ca(2+) alternans among neighboring myocytes is predominantly concordant, likely because of electrical coupling between cells. Consistent with this, partial GJ uncoupling increased propensity and amplitude of Ca(2+) alternans, and made them more sensitive to reversal by β-AR activation, as in isolated myocytes. Electrical coupling between myocytes may thus limit the alternans initiation, but also allow alternans to be more stable once established. Copyright © 2015 Elsevier Ltd. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Calcium Signaling - drug effects
Gap Junctions - drug effects
Gap Junctions - metabolism
Heart - drug effects
Heart - physiology
In Vitro Techniques -
Isoproterenol - pharmacology
Male -
Mice, Inbred C57BL -
Microscopy, Confocal -
Myocytes, Cardiac - cytology
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Receptors, Adrenergic, beta - metabolism

Find related publications in this database (Keywords)
Whole heart
beta-Adrenergic receptor activation
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