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Journal article
Enhanced basal contractility but reduced excitation-contraction coupling efficiency and β-adrenergic reserve of hearts with increased Cav1.2 activity
American journal of physiology. Heart and circulatory physiology, v 299(2), pp H519-H528
11 Jun 2010
PMID: 20543081
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Cardiac remodeling during heart failure development induces a significant increase in the activity of the L-type Ca
2+
channel (Cav1.2). However, the effects of enhanced Cav1.2 activity on myocyte excitation-contraction (E-C) coupling, cardiac contractility, and its regulation by the β-adrenergic system are not clear. To recapitulate the increased Cav1.2 activity, a double transgenic (DTG) mouse model overexpressing the Cavβ2a subunit in a cardiac-specific and inducible manner was established. We studied cardiac (in vivo) and myocyte (in vitro) contractility at baseline and upon β-adrenergic stimulation. E-C coupling efficiency was evaluated in isolated myocytes as well. The following results were found:
1
) in DTG myocytes, L-type Ca
2+
current (
I
Ca,L
) density, myocyte fractional shortening (FS), peak Ca
2+
transients, and sarcoplasmic reticulum (SR) Ca
2+
content (caffeine-induced Ca
2+
transient peak) were significantly increased (by 100.8%, 48.8%, 49.8%, and 46.8%, respectively); and
2
) cardiac contractility evaluated with echocardiography [ejection fraction (EF) and (FS)] and invasive intra-left ventricular pressure (maximum dP/d
t
and −dP/d
t
) measurements were significantly greater in DTG mice than in control mice. However,
1
) the cardiac contractility (EF, FS, dP/d
t
, and −dP/d
t
)-enhancing effect of the β-adrenergic agonist isoproterenol (2 μg/g body wt ip) was significantly reduced in DTG mice, which could be attributed to the loss of β-adrenergic stimulation on contraction, Ca
2+
transients,
I
Ca,L
, and SR Ca
2+
content in DTG myocytes; and
2
) E-C couplng efficiency was significantly lower in DTG myocytes. In conclusion, increasing Cav1.2 activity by promoting its high-activity mode enhances cardiac contractility but decreases E-C coupling efficiency and the adrenergic reserve of the heart.
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Details
- Title
- Enhanced basal contractility but reduced excitation-contraction coupling efficiency and β-adrenergic reserve of hearts with increased Cav1.2 activity
- Creators
- Mingxin Tang - Temple UniversityXiaoying Zhang - Temple UniversityYingxin Li - Temple UniversityYinzheng Guan - Temple UniversityXiaojie Ai - Temple UniversityChristopher Szeto - Temple UniversityHiroyuki Nakayama - Cincinnati Children's Hospital Medical CenterHongyu Zhang - Temple UniversityShuping Ge - St. Christopher's Hospital for ChildrenJeffery D. Molkentin - Cincinnati Children's Hospital Medical CenterSteven R. Houser - Temple UniversityXiongwen Chen - Temple University
- Publication Details
- American journal of physiology. Heart and circulatory physiology, v 299(2), pp H519-H528
- Publisher
- American Physiological Society
- Grant note
- HL-089312; HL-088243 / National Institutes of Health
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000280491100033
- Scopus ID
- 2-s2.0-77955433105
- Other Identifier
- 991019167471604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems
- Peripheral Vascular Disease
- Physiology