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

作者：Burg E D; Remillard C V; Yuan J X J^*

来源：British Journal of Pharmacology, 2008, 153(S1): S99-S111.

DOI：10.1038/sj.bjp.0707635

• pulmonary artery smooth muscle cell
• pulmonary hypertension
• apoptosis
• proliferation

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 [Ca2 ] as a result of membrane depolarization-mediated opening of voltage-dependent Ca2 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.

• 出版日期2008-3