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Overexpression of human KCNA5 increases IK V and enhances apoptosis

Elena E Brevnova1, Oleksandr Platoshyn, Shen Zhang

  • 1Division of Pulmonary and Critical Care Medicine, Dept. of Medicine, Medical Teaching Facility, University of California-San Diego, #0725, 9500 Gilman Drive, La Jolla, CA 92093-0725, USA.

American Journal of Physiology. Cell Physiology
|May 14, 2004
PubMed

Insights

Overexpressing the KCNA5 gene boosts potassium (K+) currents and enhances apoptosis, a key cell death process. This finding offers a potential strategy for treating pulmonary hypertension by promoting cell death in affected lung cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cardiovascular Research

Background:

  • Apoptotic cell shrinkage, a key indicator of apoptosis, is controlled by potassium (K+) efflux and K+ channel activity.
  • Pulmonary hypertension is linked to reduced apoptosis and K+ channels in pulmonary artery smooth muscle cells (PASMC), contributing to vascular medial hypertrophy.

Purpose of the Study:

  • To investigate if overexpressing KCNA5, which codes for a delayed-rectifier voltage-gated K+ (Kv) channel, increases K+ currents and promotes apoptosis.

Main Methods:

  • Transient transfection of KCNA5 in COS-7 cells and rat PASMC.
  • Measurement of KCNA5 protein levels and Kv channel current (I(K(V))).
  • Assessment of staurosporine (ST)-induced and basal apoptosis, caspase-3 activity, and apoptotic cell shrinkage.
  • Pharmacological blockade of KCNA5 channels using 4-aminopyridine (4-AP).

Main Results:

  • KCNA5 transfection significantly increased KCNA5 protein levels and I(K(V)) in both cell types.
  • In COS-7 cells, KCNA5 enhanced ST-induced apoptosis and caspase-3 activity but not basal apoptosis.
  • In rat PASMC, KCNA5 overexpression increased both basal and ST-induced apoptosis, accelerating apoptotic cell shrinkage.
  • 4-AP blockade reduced K+ currents and inhibited ST-induced apoptosis in KCNA5-transfected cells.

Conclusions:

  • Overexpression of the KCNA5 gene increases K+ currents, accelerates apoptotic volume decrease, elevates caspase-3 activity, and induces apoptosis.
  • KCNA5 gene transfer to induce apoptosis in PASMC presents a potential therapeutic strategy for pulmonary vascular wall thickening and idiopathic pulmonary arterial hypertension (IPAH).

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