Apoptosis repressor with caspase domain inhibits cardiomyocyte apoptosis by reducing K+ currents

Daryoush Ekhterae, Oleksandr Platoshyn, Shen Zhang, Carmelle V. Remillard, Jason Yuan

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Cell shrinkage is an early prerequisite in programmed cell death, and cytoplasmic K+ is a dominant cation that controls intracellular ion homeostasis and cell volume. Blockade of K+ channels inhibits apoptotic cell shrinkage and attenuates apoptosis. We examined whether apoptotic repressor with caspase recruitment domain (ARC), an antiapoptotic protein, inhibits cardiomyocyte apoptosis by reducing K+ efflux through voltage-gated K+ (Kv) channels. In heart-derived H9c2 cells, whole cell Kv currents (IK(V)) were isolated by using Ca2+-free extracellular (bath) solution and including 5 mM ATP and 10 mM EGTA in the intracellular (pipette) solution. Extracellular application of 5 mM 4-aminopyridine (4-AP), a blocker of Kv channels, reversibly reduced IK(V) by 50-60% in H9c2 cells. The remaining currents during 4-AP treatment may be generated by K+ efflux through 4-AP-insensitive K+ channels. Overexpression of ARC in heart-derived H9c2 cells significantly decreased IK(V), whereas treatment with staurosporine, a potent apoptosis inducer, enhanced IK(V) in wild-type cells. The staurosporine-induced increase in IK(V) was significantly suppressed and the staurosporine-mediated apoptosis was markedly inhibited in cells overexpressing ARC compared with cells transfected with the control neomycin vector. These results suggest that the antiapoptotic effect of ARC is, in part, due to inhibition of Kv channels in cardiomyocytes.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume284
Issue number6 53-6
StatePublished - Jun 1 2003
Externally publishedYes

Fingerprint

Caspases
Cardiac Myocytes
4-Aminopyridine
Staurosporine
Apoptosis
AIDS-Related Complex
Neomycin
Egtazic Acid
Cell death
Cations
Adenosine Triphosphate
Cells
Ions
Voltage-Gated Potassium Channels
Electric potential
Baths
Cell Size
Proteins
Homeostasis
Cell Death

Keywords

  • Apoptotic volume decrease
  • Cardiac myocytes
  • Potassium channels

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Apoptosis repressor with caspase domain inhibits cardiomyocyte apoptosis by reducing K+ currents. / Ekhterae, Daryoush; Platoshyn, Oleksandr; Zhang, Shen; Remillard, Carmelle V.; Yuan, Jason.

In: American Journal of Physiology - Cell Physiology, Vol. 284, No. 6 53-6, 01.06.2003.

Research output: Contribution to journalArticle

Ekhterae, Daryoush ; Platoshyn, Oleksandr ; Zhang, Shen ; Remillard, Carmelle V. ; Yuan, Jason. / Apoptosis repressor with caspase domain inhibits cardiomyocyte apoptosis by reducing K+ currents. In: American Journal of Physiology - Cell Physiology. 2003 ; Vol. 284, No. 6 53-6.
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