Ca2+ release from the sarcoplasmic reticulum activated by the low affinity Ca2+ chelator TPEN in ventricular myocytes

C. Jung, A. V. Zima, P. Szentesi, I. Jóna, L. A. Blatter, E. Niggli

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The Ca2+ content of the sarcoplasmic reticulum (SR) of cardiac myocytes is thought to play a role in the regulation and termination of SR Ca2+ release through the ryanodine receptors (RyRs). Experimentally altering the amount of Ca2+ within the SR with the membrane-permeant low affinity Ca2+ chelator TPEN could improve our understanding of the mechanism(s) by which SR Ca2+ content and SR Ca2+ depletion can influence Ca2+ release sensitivity and termination. We applied laser-scanning confocal microscopy to examine SR Ca2+ release in freshly isolated ventricular myocytes loaded with fluo-3, while simultaneously recording membrane currents using the whole-cell patch-clamp technique. Following application of TPEN, local spontaneous Ca2+ releases increased in frequency and developed into cell-wide Ca2+ waves. SR Ca2+ load after TPEN application was found to be reduced to about 60% of control. Isolated cardiac RyRs reconstituted into lipid bilayers exhibited a two-fold increase of their open probability. At the low concentration used (20-40 μM), TPEN did not significantly inhibit the SR-Ca2+-ATPase in SR vesicles. These results indicate that TPEN, traditionally used as a low affinity Ca2+ chelator in intracellular Ca2+ stores, may also act directly on the RyRs inducing an increase in their open probability. This in turn results in an increased Ca2+ leak from the SR leading to its Ca2+ depletion. Lowering of SR Ca2+ content may be a mechanism underlying the recently reported cardioprotective and antiarrhythmic features of TPEN.

Original languageEnglish
Pages (from-to)187-194
Number of pages8
JournalCell Calcium
Volume41
Issue number2
DOIs
Publication statusPublished - Feb 2007

Fingerprint

Sarcoplasmic Reticulum
Chelating Agents
Muscle Cells
Ryanodine Receptor Calcium Release Channel
N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
Membranes
Calcium-Transporting ATPases
Lipid Bilayers
Patch-Clamp Techniques
Cardiac Myocytes
Confocal Microscopy

Keywords

  • Calcium signaling
  • Cardiac muscle
  • Excitation-contraction coupling
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Cell Biology
  • Endocrinology

Cite this

Ca2+ release from the sarcoplasmic reticulum activated by the low affinity Ca2+ chelator TPEN in ventricular myocytes. / Jung, C.; Zima, A. V.; Szentesi, P.; Jóna, I.; Blatter, L. A.; Niggli, E.

In: Cell Calcium, Vol. 41, No. 2, 02.2007, p. 187-194.

Research output: Contribution to journalArticle

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