Bcl-2 decreases voltage-gated K+ channel activity and enhances survival in vascular smooth muscle cells

Daryoush Ekhterae, Oleksandr Platoshyn, Stefanie Krick, Ying Yu, Sharon S. McDaniel, Jason Yuan

Research output: Contribution to journalArticle

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Abstract

Cell shrinkage is an incipient hallmark of apoptosis in a variety of cell types. The apoptotic volume decrease has been demonstrated to attribute, in part, to K+ efflux; blockade of plasmalemmal K+ channels inhibits the apoptotic volume decrease and attenuates apoptosis. Using combined approaches of gene transfection, single-cell PCR, patch clamp, and fluorescence microscopy, we examined whether overexpression of Bcl-2, an anti-apoptotic oncoprotein, inhibits apoptosis in pulmonary artery smooth muscle cells (PASMC) by diminishing the activity of voltage-gated K+ (Kv) channels. A human bcl-2 gene was infected into primary cultured rat PASMC using an adenoviral vector. Overexpression of Bcl-2 significantly decreased the amplitude and current density of Kv currents (IKv). In contrast, the apoptosis inducer staurosporine (ST) enhanced IKv. In bcl-2-infected cells, however, the ST-induced increase in IKv was completely abolished, and the ST-induced apoptosis was significantly inhibited compared with cells infected with an empty adenovirus (-bcl-2). Blockade of Kv channels in control cells (-bcl-2) by 4-aminopyridine also inhibited the ST-induced increase in IKv and apoptosis. Furthermore, over-expression of Bcl-2 accelerated the inactivation of IKv and downregulated the mRNA expression of the pore-forming Kv channel α-subunits (Kv1.1, Kvl.5, and Kv2.1). These results suggest that inhibition of Kv channel activity may serve as an additional mechanism involved in the Bcl-2-mediated anti-apoptotic effect on vascular smooth muscle cells.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume281
Issue number1 50-1
StatePublished - 2001
Externally publishedYes

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Voltage-Gated Potassium Channels
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Staurosporine
Cells
Apoptosis
Survival
Pulmonary Artery
Genes
bcl-2 Genes
4-Aminopyridine
Fluorescence microscopy
Oncogene Proteins
Clamping devices
Fluorescence Microscopy
Adenoviridae
Transfection
Rats
Current density

Keywords

  • Apoptotic volume decrease
  • Current density of voltage-gated potassium channels
  • Pulmonary artery smooth muscle cells

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Bcl-2 decreases voltage-gated K+ channel activity and enhances survival in vascular smooth muscle cells. / Ekhterae, Daryoush; Platoshyn, Oleksandr; Krick, Stefanie; Yu, Ying; McDaniel, Sharon S.; Yuan, Jason.

In: American Journal of Physiology - Cell Physiology, Vol. 281, No. 1 50-1, 2001.

Research output: Contribution to journalArticle

Ekhterae, Daryoush ; Platoshyn, Oleksandr ; Krick, Stefanie ; Yu, Ying ; McDaniel, Sharon S. ; Yuan, Jason. / Bcl-2 decreases voltage-gated K+ channel activity and enhances survival in vascular smooth muscle cells. In: American Journal of Physiology - Cell Physiology. 2001 ; Vol. 281, No. 1 50-1.
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