Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kockskämper, J; Khafaga, M; Grimm, M; Elgner, A; Walther, S; Kockskämper, A; von Lewinski, D; Post, H; Grossmann, M; Dörge, H; Gottlieb, PA; Sachs, F; Eschenhagen, T; Schöndube, FA; Pieske, B.
Angiotensin II and myosin light-chain phosphorylation contribute to the stretch-induced slow force response in human atrial myocardium.
Cardiovasc Res. 2008; 79(4):642-651
Doi: 10.1093/cvr/cvn126
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- Führende Autor*innen der Med Uni Graz
- Khafaga Mounir
- Kockskämper Jens
- Pieske Burkert Mathias
- Co-Autor*innen der Med Uni Graz
- Kockskämper Anke
- Post Heiner
- von Lewinski Dirk
- Walther Stefanie
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- Abstract:
- Aims Stretch is an important regulator of atrial function. The functional effects of stretch on human atrium, however, are poorly understood. Thus, we characterized the stretch-induced force response in human atrium and evaluated the underlying cellular mechanisms. Methods and results Isometric twitch force of human atrial trabeculae (n = 252) was recorded (37 C, 1 Hz stimulation) following stretch from 88 (L88) to 98% (L98) of optimal length. [Na(+)](i) and pH(i) were measured using SBFI and BCECF epifluorescence, respectively. Stretch induced a biphasic force increase: an immediate increase [first-phase, Frank-Starting mechanism (FSM)] to similar to 190% of force at L88 followed by an additional slower increase [5-10 min; stow force response (SFR)] to similar to 120% of the FSM. FSM and SFR were unaffected by gender, age, ejection fraction, and pre-medication with major cardiovascular drugs. There was a positive correlation between the amplitude of the FSM and the SFR. [Na(+)](i) rose by similar to 1 mmol/L and pH(i) remained unchanged during the SFR. Inhibition of Na(+)/H(+)-exchange (3 mu M HOE642), Na(+)/Ca(2+)-exchange (5 mu M KB-R7943), or stretch-activated channels (0.5 mu M, GsMtx-4 and 80 mu M streptomycin) did not reduce the SFR. Inhibition of angiotensin-II (AngII) receptors (5 mu M saralasin and 0.5 mu M PD123319) or pre-application of 0.5 mu M AngII, however, reduced the SFR by similar to 40-60%. Moreover, stretch increased phosphorylation of myosin tight chain 2 (MLC2a) and inhibition of MLC kinase (10 mu M ML-7 and 5 mu M wortmannin) decreased the SFR by similar to 40-85%. Conclusion Stretch elicits a SFR in human atrium. The atrial SFR is mediated by stretch-induced release and autocrine/paracrine actions of AngII and increased myofilament Ca(2+) responsiveness via phosphorylation of MLC2a by MLC kinase.
- Find related publications in this database (using NLM MeSH Indexing)
- Angiotensin II - metabolism
- Atrial Appendage - metabolism
- Cardiac Myosins - metabolism
- Cell Size -
- Humans -
- Hydrogen-Ion Concentration -
- Ion Channels - metabolism
- Isometric Contraction -
- Kinetics -
- Mechanotransduction, Cellular - drug effects
- Models, Biological -
- Muscle Strength -
- Myocardial Contraction - drug effects
- Myocardium - enzymology Myocardium - metabolism
- Myosin Light Chains - metabolism
- Myosin-Light-Chain Kinase - metabolism
- Phosphorylation -
- Reflex, Stretch -
- Reproducibility of Results -
- Saralasin - pharmacology
- Sodium - metabolism
- Sodium-Calcium Exchanger - metabolism
- Sodium-Hydrogen Antiporter - metabolism
- Find related publications in this database (Keywords)
- stretch
- human
- atrium
- force
- angiotensin II