title: Bcl-2 decreases voltage-gated K+ channel activity and enhances survival in vascular smooth muscle cells.
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 (I(Kv)). In contrast, the apoptosis inducer staurosporine (ST) enhanced I(Kv). In bcl-2-infected cells, however, the ST-induced increase in I(Kv) 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 I(Kv) and apoptosis. Furthermore, overexpression of Bcl-2 accelerated the inactivation of I(Kv) and downregulated the mRNA expression of the pore-forming Kv channel alpha-subunits (Kv1.1, Kv1.5, 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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California School of Medicine, San Diego, California 92103, USA.
authors.forename: D
authors.initials: D
authors.lastname: Ekhterae
authors.forename: O
authors.initials: O
authors.lastname: Platoshyn
authors.forename: S
authors.initials: S
authors.lastname: Krick
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.forename: S S
authors.initials: SS
authors.lastname: McDaniel
authors.forename: J X
authors.initials: JX
authors.lastname: Yuan
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D015640:Ion Channel Gating; D008168:Lung / Q000098:blood supply; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019253:Proto-Oncogene Proteins c-bcl-2; D015761:4-Aminopyridine; D020169:Caspases; D019311:Staurosporine