Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Hohendanner, F; Ljubojević, S; MacQuaide, N; Sacherer, M; Sedej, S; Biesmans, L; Wakula, P; Platzer, D; Sokolow, S; Herchuelz, A; Antoons, G; Sipido, K; Pieske, B; Heinzel, FR.
Intracellular dyssynchrony of diastolic cytosolic [Ca²⁺] decay in ventricular cardiomyocytes in cardiac remodeling and human heart failure.
Circ Res. 2013; 113(5):527-38
Doi: 10.1161/CIRCRESAHA.113.300895
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
- Heinzel Frank
- Co-authors Med Uni Graz
- Holzer Senka
- Pieske Burkert Mathias
- Platzer Dieter
- Sacherer Michael
- Sedej Simon
- Wakula-Heinzel Paulina
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- RATIONALE: Synchronized release of Ca²⁺ into the cytosol during each cardiac cycle determines cardiomyocyte contraction. OBJECTIVE: We investigated synchrony of cytosolic [Ca²⁺] decay during diastole and the impact of cardiac remodeling. METHODS AND RESULTS: Local cytosolic [Ca²⁺] transients (1-µm intervals) were recorded in murine, porcine, and human ventricular single cardiomyocytes. We identified intracellular regions of slow (slowCaR) and fast (fastCaR) [Ca²⁺] decay based on the local time constants of decay (TAUlocal). The SD of TAUlocal as a measure of dyssynchrony was not related to the amplitude or the timing of local Ca²⁺ release. Stimulation of sarcoplasmic reticulum Ca²⁺ ATPase with forskolin or istaroxime accelerated and its inhibition with cyclopiazonic acid slowed TAUlocal significantly more in slowCaR, thus altering the relationship between SD of TAUlocal and global [Ca²⁺] decay (TAUglobal). Na⁺/Ca²⁺ exchanger inhibitor SEA0400 prolonged TAUlocal similarly in slowCaR and fastCaR. FastCaR were associated with increased mitochondrial density and were more sensitive to the mitochondrial Ca²⁺ uniporter blocker Ru360. Variation in TAUlocal was higher in pig and human cardiomyocytes and higher with increased stimulation frequency (2 Hz). TAUlocal correlated with local sarcomere relengthening. In mice with myocardial hypertrophy after transverse aortic constriction, in pigs with chronic myocardial ischemia, and in end-stage human heart failure, variation in TAUlocal was increased and related to cardiomyocyte hypertrophy and increased mitochondrial density. CONCLUSIONS: In cardiomyocytes, cytosolic [Ca²⁺] decay is regulated locally and related to local sarcomere relengthening. Dyssynchronous intracellular [Ca²⁺] decay in cardiac remodeling and end-stage heart failure suggests a novel mechanism of cellular contractile dysfunction.
- Find related publications in this database (using NLM MeSH Indexing)
- Aniline Compounds - pharmacology
- Animals - administration & dosage
- Calcium Signaling - drug effects, physiology
- Calcium-Transporting ATPases - antagonists & inhibitors, metabolism
- Colforsin - pharmacology
- Cytosol - metabolism
- Diastole - administration & dosage
- Electric Stimulation - administration & dosage
- Etiocholanolone - analogs & derivatives, pharmacology
- Heart Failure - physiopathology
- Heart Ventricles - cytology
- Humans - administration & dosage
- Hypertrophy - administration & dosage
- Hypertrophy, Left Ventricular - physiopathology
- Indoles - pharmacology
- Mice - administration & dosage
- Mitochondria, Heart - drug effects, metabolism
- Myocardial Ischemia - physiopathology
- Myocytes, Cardiac - drug effects, pathology, physiology
- Phenyl Ethers - pharmacology
- Ruthenium Compounds - pharmacology
- Sarcomeres - ultrastructure
- Sarcoplasmic Reticulum - drug effects, enzymology
- Sodium-Calcium Exchanger - antagonists & inhibitors, genetics
- Sus scrofa - administration & dosage
- Swine - administration & dosage
- Ventricular Remodeling - physiology
- Find related publications in this database (Keywords)
- calcium
- diastole
- heart failure
- mitochondria
- myocytes, cardiac
- ventricular remodeling