Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Maier, LS; Wahl-Schott, C; Horn, W; Weichert, S; Pagel, C; Wagner, S; Dybkova, N; Müller, OJ; Näbauer, M; Franz, WM; Pieske, B.
Increased SR Ca2+ cycling contributes to improved contractile performance in SERCA2a-overexpressing transgenic rats.
Cardiovasc Res. 2005; 67(4):636-646
Doi: 10.1016/j.cardiores.2005.05.006
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- Co-Autor*innen der Med Uni Graz
- Pieske Burkert Mathias
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- Abstract:
- OBJECTIVE: Heart failure is associated with reduced function of sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) but increased function of sarcolemmal Na+/Ca2+ exchanger (NCX), leading to decreased SR Ca2+ content and loss of frequency-potentiation of contractile force. We reported that SERCA2a-overexpression in transgenic rat hearts (TG) results in improved contractility. However, it was not clear whether TG have improved contractility due to frequency-dependent improved SR Ca2+ handling. METHODS: Therefore, we characterized TG (n=35) vs. wild-type (WT) control rats (n=39) under physiological conditions (37 degrees C, stimulation rate <8 Hz). Twitch force, intracellular Ca2+ transients ([Ca2+]i), and SR Ca2+ content were measured in isolated muscles. The contribution of transsarcolemmal Ca2+ influx (I(Ca)) through L-type Ca2+ channels (LTCC) and reverse mode NCX (I(Na/Ca)) to Ca2+ cycling were studied in isolated myocytes. RESULTS: With increasing frequency, force increased in TG muscles by 168+/-35% (8 Hz; P<0.05) and SR Ca2+ content increased by maximally 118+/-31% (4 Hz; P<0.05). In WT, there was a flat force-frequency response without changes in SR Ca2+ content. Relaxation parameters of force and [Ca2+]i decay were accelerated at each frequency in TG vs. WT by approximately 10%. At prolonged rest intervals (<240 s), force and SR Ca2+ content increased significantly more in TG. Consequently, absolute SR Ca2+ content measured in myocytes was increased approximately 2-fold in TG. Transsarcolemmal Ca2+ fluxes estimated by I(Ca) (at 0 mV -10.2+/-1.1 vs. -16.9+/-1.3 pA/pF) and I(Na/Ca) (0.17+/-0.02 vs. 0.46+/-0.05 pA/pF) were decreased in TG vs. WT (P<0.05), whereas NCX and LTCC protein expression was only slightly reduced (P=n.s.). CONCLUSION: In summary, SERCA2a-overexpression improved contractility in a frequency-dependent way due to increased SR Ca2+ loading whereas transsarcolemmal Ca2+ fluxes were decreased.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Animals, Genetically Modified -
- Blotting, Western - methods
- Calcium - metabolism
- Calcium Channels, L-Type - metabolism
- Calcium-Transporting ATPases - metabolism
- Electric Stimulation - metabolism
- Heart Failure, Congestive - metabolism
- Myocardial Contraction - physiology
- Myocytes, Cardiac - metabolism
- Patch-Clamp Techniques - metabolism
- Rats - metabolism
- Sarcolemma - metabolism
- Sarcoplasmic Reticulum - metabolism
- Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism
- Sodium-Calcium Exchanger - metabolism
- Find related publications in this database (Keywords)
- calcium (cellular)
- contractile function
- E-C coupling
- transgenic animal models
- SR (function)