Potassium channels in the regulation of pulmonary artery smooth muscle cell proliferation and apoptosis: Pharmacotherapeutic implications

E. D. Burg, C. V. Remillard, J. X.J. Yuan

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Maintaining the proper balance between cell apoptosis and proliferation is required for normal tissue homeostasis; when this balance is disrupted, disease such as pulmonary arterial hypertension (PAH) can result. Activity of K + channels plays a major role in regulating the pulmonary artery smooth muscle cell (PASMC) population in the pulmonary vasculature, as they are involved in cell apoptosis, survival and proliferation. PASMCs from PAH patients demonstrate many cellular abnormalities linked to K + channels, including decreased K + current, downregulated expression of various K + channels, and inhibited apoptosis. K + is the major intracellular cation, and the K + current is a major determinant of cell volume. Apoptotic volume decrease (AVD), an early hallmark and prerequisite of programmed cell death, is characterized by K + and Cl - efflux. In addition to its role in AVD, cytosolic K + can be inhibitory toward endogenous caspases and nucleases and can suppress mitochondrial cytochrome c release. In PASMC, K + channel activation accelerates AVD and enhances apoptosis, while K + channel inhibition decelerates AVD and inhibits apoptosis. Finally, inhibition of K + channels, by increasing cytosolic [Ca 2+] as a result of membrane depolarization-mediated opening of voltage-dependent Ca 2+ channels, leads to PASMC contraction and proliferation. The goals of this review are twofold: (1) to elucidate the role of K + ions and K + channels in the proliferation and apoptosis of PASMC, with an emphasis on abnormal cell growth in human and animal models of PAH, and (2) to elaborate upon the targeting of K + flux pathways for pharmacological treatment of pulmonary vascular disease.

Original languageEnglish (US)
Pages (from-to)S99-S111
JournalBritish Journal of Pharmacology
Volume153
Issue numberSUPPL. 1
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

Keywords

  • Apoptosis
  • Proliferation
  • Pulmonary artery smooth muscle cell
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Pharmacology

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