Mechanosensitivity of microdomain calcium signalling in the heart. (November 2017)

• Record Type: Journal Article
• Authors: Schönleitner, Patrick; Schotten, Uli; Antoons, Gudrun
• Is Part Of: Progress in biophysics and molecular biology. Volume 130:Part B(2017)
• Page Start: 288
• Page End: 301
• Publication Date: 2017-11
• Subjects: Preload -- Afterload -- Calcium sparks -- Microdomains -- Mechanotransduction -- Stretch-induced arrhythmias; AP action potential -- AT axial tubule -- Ca2+ calcium -- CaMKII Ca2+/calmodulin-dependent protein kinase II -- CICR Ca2+ induced Ca2+ release -- GSMTx4 Grammostola spatulata mechanotoxin-4 -- IP3 inositol 1, 4, 5-trisphosphate -- LTCC L-type Ca2+ channel -- MCU mitochondrial Ca2+ uniporter -- α-MHC alpha-myosin heavy chain -- Na+ sodium -- NCX Na+/Ca2+ -exchanger -- NHE1 Na+/H+ -Exchanger 1 -- NO nitric oxide -- NOS nitric oxide synthase -- eNOS endothelial nitric oxide synthase -- nNOS neuronal nitric oxide synthase -- NOX2 NADPH Oxidase Type 2 -- ROS reactive oxygen species -- RyR ryanodine receptor -- SAC stretch activated channel -- SERCA sarco/endoplasmic reticulum Ca2+-ATPase -- SR sarcoplasmic reticulum -- TnC troponin C -- TT transverse tubule -- AT axial tubule; Biophysics -- Periodicals; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular Biology -- Periodicals; Biophysique -- Périodiques; Biochimie -- Périodiques; 571.4
• DOI: 10.1016/j.pbiomolbio.2017.06.013
• Languages: English
• ISSNs: 0079-6107

Abstract

Abstract: In cardiac myocytes, calcium (Ca 2+ ) signalling is tightly controlled in dedicated microdomains. At the dyad, i.e. the narrow cleft between t-tubules and junctional sarcoplasmic reticulum (SR), many signalling pathways combine to control Ca 2+ -induced Ca 2+ release during contraction. Local Ca 2+ gradients also exist in regions where SR and mitochondria are in close contact to regulate energetic demands. Loss of microdomain structures, or dysregulation of local Ca 2+ fluxes in cardiac disease, is often associated with oxidative stress, contractile dysfunction and arrhythmias. Ca 2+ signalling at these microdomains is highly mechanosensitive. Recent work has demonstrated that increasing mechanical load triggers rapid local Ca 2+ releases that are not reflected by changes in global Ca 2+ . Key mechanisms involve rapid mechanotransduction with reactive oxygen species or nitric oxide as primary signalling molecules targeting SR or mitochondria microdomains depending on the nature of the mechanical stimulus. This review summarizes the most recent insights in rapid Ca 2+ microdomain mechanosensitivity and re-evaluates its (patho)physiological significance in the context of historical data on the macroscopic role of Ca 2+ in acute force adaptation and mechanically-induced arrhythmias. We distinguish between preload and afterload mediated effects on local Ca 2+ release, and highlight differences between atrial and ventricular myocytes. Finally, we provide an outlook for further investigation in chronic models of abnormal mechanics (eg post-myocardial infarction, atrial fibrillation), to identify the clinical significance of disturbed Ca 2+ mechanosensitivity for arrhythmogenesis.