Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Schmidt, AG; Kadambi, VJ; Ball, N; Sato, Y; Walsh, RA; Kranias, EG; Hoit, BD.
Cardiac-specific overexpression of calsequestrin results in left ventricular hypertrophy, depressed force-frequency relation and pulsus alternans in vivo.
J Mol Cell Cardiol. 2000; 32(9): 1735-1744.
Doi: 10.1006/jmcc.2000.1209
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Schmidt Albrecht
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- Abstract:
- Cardiac-specific overexpression of calsequestrin has been shown to result in significant decreases in contractile parameters and intracellular Ca(2+)transients in vitro. Therefore, the purpose of the present study was to determine the effects of calsequestrin overexpression on basal cardiac function and the force-frequency relation in vivo. Calsequestrin overexpression mice (CSQ-OE, n=20) and their isogenic controls (WT) were studied with an integrative approach using transthoracic echocardiography, stress-shortening relations, and invasive hemodynamics in intact closed-chest mice. M-mode echocardiography indicated that calsequestrin overexpression resulted in concentric hypertrophy (+52%) and an increase in LV ejection phase indices. However, mean end-systolic stress-shortening coordinates revealed that at matched end-systolic wall-stress, fractional shortening was depressed in CSQ-OE mice. This was confirmed by depressed indices of LV isovolumic contraction and relaxation in CSQ-OE v. WT mice. Furthermore, overexpression of calsequestrin resulted in a downward and leftward shift of the biphasic force-frequency relation; thus, the critical heart (HR(crit)) was significantly lower in calsequestrin-overexpression mice (264+/-15 bpm) than in wild-type controls (365+/-21 bpm). Surprisingly, calsequestrin overexpression was associated with the induction of pulsus alternans in every animal (at an average heart rate of 428+/-26 bpm), whereas none of the wild-type controls displayed this phenomenon. We conclude that: (i) although increased levels of calsequestrin result in decreased myocardial contractility and a depressed force-frequency relation, LV wall stress is reduced and chamber function is normal, and (ii) an increase in SR Ca(2+)storage capacity induces pulsus alternans in the intact anesthetized mouse.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Calsequestrin - physiology
- Echocardiography -
- Gene Expression -
- Hemodynamics -
- Hypertrophy, Left Ventricular - etiology Hypertrophy, Left Ventricular - physiopathology
- Mice -
- Mice, Transgenic -
- Myocardial Contraction -
- Find related publications in this database (Keywords)
- calsequestrin
- force-frequency relation
- transgenic mice
- hemodynamics
- echocardiography