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Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
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Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes

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Altered interaction of FKBP12.6 with ryanodine receptor as a cause of abnormal Ca(2+) release in heart failure

K Ono1, M Yano, T Ohkusa

  • 1Second Department of Internal Medicine, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, 755-8505, Yamaguchi, Japan.

Cardiovascular Research
|October 31, 2000
PubMed

Insights

In heart failure, FK binding protein (FKBP) levels significantly decrease, impairing sarcoplasmic reticulum calcium release. This reduction in FKBP contributes to ryanodine receptor instability and cardiac dysfunction.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Physiology

Background:

  • Sarcoplasmic reticulum (SR) Ca(2+) release is crucial for cardiac function.
  • The role of FK binding protein (FKBP) in modulating cardiac ryanodine receptor (RyR) gating in heart failure is not well understood.

Purpose of the Study:

  • To investigate the Ca(2+) release function of the SR in heart failure.
  • To determine if alterations in FKBP are associated with changes in SR Ca(2+) release in heart failure.

Main Methods:

  • SR vesicles were isolated from normal and pacing-induced heart failure (HF) dog models.
  • SR Ca(2+) release kinetics were measured using stopped-flow apparatus.
  • [3H]ryanodine and [3H]dihydro-FK506 binding assays were performed.

Main Results:

  • Heart failure significantly reduced the number of FKBPs bound to RyR by 83%.
  • FK506, which dissociates FKBP from RyR, impaired Ca(2+) release in normal but not HF SR.
  • The rate of Ca(2+) release from HF SR was 61% lower than in normal SR.

Conclusions:

  • A significant decrease in FKBP in heart failure may lead to RyR channel instability.
  • Impaired SR Ca(2+) release function in heart failure is linked to reduced FKBP levels.
  • These findings highlight FKBP as a potential therapeutic target in heart failure.
Abstract

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