| Autor: |
Justin G. Lichter, John H.B. Bridge, Robin Moss, Thomas Seidel, Frank B. Sachse, Hui Li |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
Biophysical Journal. 108(2) |
| ISSN: |
0006-3495 |
| DOI: |
10.1016/j.bpj.2014.11.1441 |
| Popis: |
Dyssynchronous heart failure (DHF) is associated with structural and functional remodeling in cardiomyocytes from subcellular to whole organ level. Several studies have demonstrated remodeling of Ca2+ signaling and excitation-contraction coupling. This study aimed at quantification of the subcellular spatial distribution of diastolic local Ca2+ release events (sparks) in cardiomyocytes and their remodeling in DHF.Adult canines were used as control and DHF models. DHF was induced by right ventricular tachypacing at 200 beats per minute. Left ventricular cardiomyocytes were isolated via enzymatic digestion, loaded with Fluo-4 and Di-8-ANEPPS, and imaged with rapid scanning confocal microscopy (Zeiss LSM 5 Duo). Acquisition of 2D image sequences was initiated 460 ms after stimulation of the myocytes. Images were acquired at a xy resolution of 0.1 µm with a field of view of 102.4 µm (x) x 25.6 µm (y). Image sequences comprised 100 frames at 9.3 ms per frame. Image analysis involved cell segmentation and spark detection. We compared spark density in regions 0-10 µm and 10-40 µm from the longitudinal cell end.Our analyses yielded a similar diastolic spark density in control and DHF cells (0.0119 ± 0.0023 vs 0.0155 ± 0.0027 sparks/µm2/s, respectively). In control cells spark density was homogeneously distributed. In contrast, DHF cells exhibited a decreased spark density within 0-10 µm versus 10-40 µm from the longitudinal cell end (0.0101 ± 0.0039 vs 0.0227 ± 0.0047 sparks/µm2/s, respectively).DHF is associated with a spatially heterogeneous remodeling of spark density. This finding provides a foundation for understanding basic mechanisms of arrhythmogenesis in heart failure cells. The heterogeneity of spark density may result from heterogeneous structural remodeling, for instance, remodeling of ryanodine receptor clusters and the transverse tubular system. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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