Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kockskämper, J; von Lewinski, D; Khafaga, M; Elgner, A; Grimm, M; Eschenhagen, T; Gottlieb, PA; Sachs, F; Pieske, B.
The slow force response to stretch in atrial and ventricular myocardium from human heart: functional relevance and subcellular mechanisms.
Prog Biophys Mol Biol. 2008; 97(2-3): 250-267.
Doi: 10.1016/j.pbiomolbio.2008.02.026
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- Führende Autor*innen der Med Uni Graz
- Kockskämper Jens
- Pieske Burkert Mathias
- Co-Autor*innen der Med Uni Graz
- Khafaga Mounir
- von Lewinski Dirk
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- Abstract:
- Mechanical load is an important regulator of cardiac force. Stretching human atrial and ventricular trabeculae elicited a biphasic force increase: an immediate increase (Frank-Starling mechanism) followed by a further slow increase (slow force response, SFR). In ventricle, the SFR was unaffected by AT- and ET-receptor antagonism, by inhibition of protein-kinase-C, PI-3-kinase, and NO-synthase, but attenuated by inhibition of Na+/H+- (NHE) and Na+/Ca2+ exchange (NCX). In atrium, however, neither NHE- nor NCX-inhibition affected the SFR. Stretch elicited a large NHE-dependent [Na+]i increase in ventricle but only a small, NHE-independent [Na+]i increase in atrium. Stretch-activated non-selective cation channels contributed to basal force development in atrium but not ventricle and were not involved in the SFR in either tissue. Interestingly, inhibition of AT receptors or pre-application of angiotensin II or endothelin-1 reduced the atrial SFR. Furthermore, stretch increased phosphorylation of atrial myosin light chain 2 (MLC2) and inhibition of myosin light chain kinase (MLCK) attenuated the SFR in atrium and ventricle. Thus, in human heart both atrial and ventricular myocardium exhibit a stretch-dependent SFR that might serve to adjust cardiac output to increased workload. In ventricle, there is a robust NHE-dependent (but angiotensin II- and endothelin-1-independent) [Na+]i increase that is translated into a [Ca2+]i and force increase via NCX. In atrium, on the other hand, there is an angiotensin II- and endothelin-dependent (but NHE- and NCX-independent) force increase. Increased myofilament Ca2+ sensitivity through MLCK-induced phosphorylation of MLC2 is a novel mechanism contributing to the SFR in both atrium and ventricle.
- Find related publications in this database (using NLM MeSH Indexing)
- Angiotensin II - metabolism
- Cardiac Myosins - metabolism
- Endothelin-1 - metabolism
- Heart - physiology
- Heart Atria - metabolism
- Humans -
- Myocardial Contraction - physiology
- Myocardium - metabolism
- Myosin Light Chains - metabolism
- Nitric Oxide Synthase - metabolism
- Protein Kinase C - metabolism
- Sarcoplasmic Reticulum - physiology
- Sodium-Calcium Exchanger - metabolism
- Sodium-Hydrogen Antiporter - metabolism
- Stress, Mechanical -
- Ventricular Function -
- Find related publications in this database (Keywords)
- stretch
- human myocardium
- slow force response
- atrium
- ventricle
- sodium