What question did this study set out to answer?

To determine the role of human FK-506–binding protein 12.0 (FKBP12.0) overexpression on cardiac excitation–contraction coupling in adult rabbit ventricular myocytes.

September 14, 2007ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam)

Overexpression of FK-506–Binding Protein 12.0 Modulates Excitation–Contraction Coupling in Adult Rabbit Ventricular Cardiomyocytes

Q: What is the clinical evidence from this study?

Intervention: Overexpression of FKBP12.0 via Ad-FKBP12.0 transfection. Primary outcome: Cardiac excitation-contraction coupling parameters (Ca2+ transient amplitude, sarcoplasmic reticulum Ca2+ load, Ca2+ spark morphology).

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Key result

Overexpression of FKBP12.0 in adult rabbit ventricular cardiomyocytes increased sarcoplasmic reticulum Ca2+ load by approximately 25% and reduced the sensitivity of RyR2 to Ca2+.

Population

Adult rabbit ventricular cardiomyocytes (and proteins isolated from human, rabbit, and dog myocardium)

Design

Preclinical

Authors

TSTim SeidlerInterventional / Structural Cardiology CLChristopher M. LoughreyElectrophysiology DZDarya ZibrovaJena University Hospital

Discussion

Member takes

Implication

Hypothesis-generating for FKBP12.0 modulation of RyR2 in cardiomyocytes; human validation required before any clinical consideration.

Key Points

To determine the role of human FK-506–binding protein 12.0 (FKBP12.0) overexpression on cardiac excitation–contraction coupling in adult rabbit ventricular myocytes.
Adult rabbit ventricular myocytes were transfected with an adenoviral vector encoding human FKBP12.0 (Ad-FKBP12.0).
FKBP12.0 expression and binding to ryanodine receptor 2 (RyR2) were evaluated using Western blotting, co-immunoprecipitation, and glutathione S-transferase pull-down assays.
L-type Ca2+ current, Na+/Ca2+ exchanger activity, sarcoplasmic reticulum Ca2+ load, and permeabilized Ca2+ spark parameters were quantified using voltage-clamp and confocal microscopy.
Adenoviral transfection increased FKBP12.0 expression by 2.6 ± 0.4-fold (n=5) and demonstrated RyR2 binding in rabbit and human myocardium without altering L-type Ca2+ currents or Na+/Ca2+ exchanger efflux.
FKBP12.0 overexpression increased sarcoplasmic reticulum Ca2+ load by approximately 25% while decreasing the trigger efficiency of L-type Ca2+ currents, indicating reduced RyR2 Ca2+ sensitivity.
In permeabilized myocytes, FKBP12.0 overexpression significantly increased Ca2+ spark amplitude and duration while decreasing spark frequency.

Structured PICO

Population

Adult rabbit ventricular cardiomyocytes (and proteins isolated from human, rabbit, and dog myocardium)

Intervention

Transfection with a recombinant adenovirus coding for human FKBP12.0 (Ad-FKBP12.0)

Outcome

Cardiac excitation-contraction coupling parameters including L-type Ca2+ current, Ca2+ efflux rates, Ca2+ transient amplitude, sarcoplasmic reticulum Ca2+ load, and Ca2+ spark morphologysurrogate

Overexpression of FKBP12.0 in adult rabbit ventricular cardiomyocytes reduces RyR2 Ca2+ sensitivity and regulates the gain of excitation-contraction coupling.

Cite This Study

Seidler et al. (2007) studied this question. Overexpression of FKBP12.0 via Ad-FKBP12.0 transfection was evaluated on Cardiac excitation-contraction coupling parameters (Ca2+ transient amplitude, sarcoplasmic reticulum Ca2+ load, Ca2+ spark morphology). Overexpression of FKBP12.0 in adult rabbit ventricular cardiomyocytes increased sarcoplasmic reticulum Ca2+ load by approximately 25% and reduced the sensitivity of RyR2 to Ca2+.

synapsesocial.com/papers/6a96252c538affa4349febe8 https://doi.org/10.1161/circresaha.107.154609

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Overexpression of FK-506–Binding Protein 12.0 Modulates Excitation–Contraction Coupling in Adult Rabbit Ventricular Cardiomyocytes

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Overexpression of FK-506–Binding Protein 12.0 Modulates Excitation–Contraction Coupling in Adult Rabbit Ventricular Cardiomyocytes

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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