Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.1016/j.yjmcc.2015.03.012
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- Co-Autor*innen der Med Uni Graz
- Holzer Senka
- Pieske Burkert Mathias
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- Abstract:
- 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)
- Calcium
- Whole heart
- Alternans
- beta-Adrenergic receptor activation