Potassium channels and apoptosis

Application to pulmonary vascular disease

Amy L. Firth, Amanda White, Jason Yuan

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

A fine balance between cell proliferation and apoptosis is critical to maintain normal tissue homeostasis. An imbalance in proliferative and apoptotic rates is the underlying pathophysiology of many disease states including cancer, neurodegenerative diseases and pulmonary vascular disease. Pulmonary arterial hypertension (PAH), for example, is a disease characterized by sustained elevated pulmonary vascular resistance and pulmonary arterial pressure. A contributory pathophysiological process is progressive pulmonary vascular remodeling, primarily due to an increased proliferative potential and decreased apoptotic rate in pulmonary artery smooth muscle cells in the medial layer of pulmonary arteries. A key hallmark of apoptosis is a two-phase cell shrinkage with apoptotic volume decrease (AVD) being the early phase. Intracellular ion homeostasis, determined by the activity of plasma membrane ion channels and transporters, is the predominant mechanism regulating this early phase. During homeostasis cytoplasmic cation K+ (140 mM) and anion Cl (50-100 mM) concentration is high; this electrochemical gradient drives an efflux of K+ upon opening of plasmalemmal K+ channels and initiates AVD. To equilibrate the imbalance created between intracellular and extracellular osmolarity with the extrusion of K+ and Cl, water leaves the cell through aquaporins causing cell shrinkage. This early stage is a prerequisite for later phases of apoptosis including DNA fragmentation, caspase activation and mitochondrial membrane depolarization. Furthermore, the decreased intracellular K+ concentration relieves the inhibition of endogenous caspases and nucleases; nuclease induced chromatin fragmentation is able to occur. Finally, this leads to the formation and eventual phagocytosis of apoptotic bodies by macrophages. K+ channels have inherent roles in both the early and late phases of apoptosis. This chapter describes the involvement of K+ channels in apoptotic mechanisms, in particular as they pertain to pulmonary arterial hypertension.

Original languageEnglish (US)
Title of host publicationApoptosis
Subtitle of host publicationModern Insights into Disease from Molecules to Man
PublisherCRC Press
Pages355-3702
Number of pages3348
ISBN (Electronic)9781439845431
ISBN (Print)9781578085835
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Fingerprint

Potassium Channels
Vascular Diseases
Lung Diseases
Apoptosis
Homeostasis
Caspases
Ion Channels
Pulmonary Hypertension
Pulmonary Artery
Tissue homeostasis
Neurodegenerative diseases
Lung
Aquaporins
Membrane Transport Proteins
Macrophages
Depolarization
Cell proliferation
Mitochondrial Membranes
DNA Fragmentation
Cell membranes

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Firth, A. L., White, A., & Yuan, J. (2010). Potassium channels and apoptosis: Application to pulmonary vascular disease. In Apoptosis: Modern Insights into Disease from Molecules to Man (pp. 355-3702). CRC Press. https://doi.org/10.1201/9781439845431

Potassium channels and apoptosis : Application to pulmonary vascular disease. / Firth, Amy L.; White, Amanda; Yuan, Jason.

Apoptosis: Modern Insights into Disease from Molecules to Man. CRC Press, 2010. p. 355-3702.

Research output: Chapter in Book/Report/Conference proceedingChapter

Firth, AL, White, A & Yuan, J 2010, Potassium channels and apoptosis: Application to pulmonary vascular disease. in Apoptosis: Modern Insights into Disease from Molecules to Man. CRC Press, pp. 355-3702. https://doi.org/10.1201/9781439845431
Firth AL, White A, Yuan J. Potassium channels and apoptosis: Application to pulmonary vascular disease. In Apoptosis: Modern Insights into Disease from Molecules to Man. CRC Press. 2010. p. 355-3702 https://doi.org/10.1201/9781439845431
Firth, Amy L. ; White, Amanda ; Yuan, Jason. / Potassium channels and apoptosis : Application to pulmonary vascular disease. Apoptosis: Modern Insights into Disease from Molecules to Man. CRC Press, 2010. pp. 355-3702
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