Beta-Adrenoceptor Stimulation Reveals Ca2+ Waves and Sarcoplasmic Reticulum Ca2+ Depletion in Left Ventricular Cardiomyocytes from Post-Infarction Rats with and without Heart Failure

Autor: Ivar Sjaastad, Karina Hougen, Jan Magnus Aronsen, Mathis K. Stokke, Mani Sadredini, Ravinea Manotheepan, Tore K. Danielsen
Rok vydání: 2015
Předmět:
0301 basic medicine
Male
Myocardial Infarction
lcsh:Medicine
Stimulation
030204 cardiovascular system & hematology
Biochemistry
0302 clinical medicine
Animal Cells
Diastole
Medicine and Health Sciences
Myocyte
Myocytes
Cardiac
Wave Frequency
Myocardial infarction
Post-Translational Modification
Phosphorylation
lcsh:Science
Cells
Cultured
Multidisciplinary
Physics
Heart
Sarcoplasmic Reticulum
Physical Sciences
Cardiology
Cellular Types
Anatomy
Arrhythmia
Research Article
Cardiac function curve
medicine.medical_specialty
Heart Ventricles
Muscle Tissue
03 medical and health sciences
Internal medicine
Receptors
Adrenergic
beta
medicine
Animals
Calcium Signaling
Rats
Wistar
Heart Failure
Muscle Cells
business.industry
Endoplasmic reticulum
lcsh:R
Biology and Life Sciences
Proteins
Arrhythmias
Cardiac
Cell Biology
medicine.disease
Myocardial Contraction
030104 developmental biology
Biological Tissue
Heart failure
Cardiovascular Anatomy
Waves
lcsh:Q
Calcium
business
Homeostasis
Zdroj: PLoS ONE
PLoS ONE, Vol 11, Iss 4, p e0153887 (2016)
ISSN: 1932-6203
Popis: Abnormal cellular Ca2+ handling contributes to both contractile dysfunction and arrhythmias in heart failure. Reduced Ca2+ transient amplitude due to decreased sarcoplasmic reticulum Ca2+ content is a common finding in heart failure models. However, heart failure models also show increased propensity for diastolic Ca2+ release events which occur when sarcoplasmic reticulum Ca2+ content exceeds a certain threshold level. Such Ca2+ release events can initiate arrhythmias. In this study we aimed to investigate if both of these aspects of altered Ca2+ homeostasis could be found in left ventricular cardiomyocytes from rats with different states of cardiac function six weeks after myocardial infarction when compared to sham-operated controls. Video edge-detection, whole-cell Ca2+ imaging and confocal line-scan imaging were used to investigate cardiomyocyte contractile properties, Ca2+ transients and Ca2+ waves. In baseline conditions, i.e. without beta-adrenoceptor stimulation, cardiomyocytes from rats with large myocardial infarction, but without heart failure, did not differ from sham-operated animals in any of these aspects of cellular function. However, when exposed to beta-adrenoceptor stimulation, cardiomyocytes from both non-failing and failing rat hearts showed decreased sarcoplasmic reticulum Ca2+ content, decreased Ca2+ transient amplitude, and increased frequency of Ca2+ waves. These results are in line with a decreased threshold for diastolic Ca2+ release established by other studies. In the present study, factors that might contribute to a lower threshold for diastolic Ca2+ release were increased THR286 phosphorylation of Ca2+/calmodulin-dependent protein kinase II and increased protein phosphatase 1 abundance. In conclusion, this study demonstrates both decreased sarcoplasmic reticulum Ca2+ content and increased propensity for diastolic Ca2+ release events in ventricular cardiomyocytes from rats with heart failure after myocardial infarction, and that these phenomena are also found in rats with large myocardial infarctions without heart failure development. Importantly, beta-adrenoceptor stimulation is necessary to reveal these perturbations in Ca2+ handling after a myocardial infarction.
Databáze: OpenAIRE
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