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 X.J. Yuan

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

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)
Pages (from-to)C157-C165
JournalAmerican Journal of Physiology - Cell Physiology
Volume281
Issue number1 50-1
DOIs
StatePublished - 2001

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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