Commentary Cellscience Reviews Vol.2 No.4 ISSN 1742-8130

A Lethal Move: Surfacing of Kv2.1 Channel and Induction of Apoptosis

Abstract

Programmed cell death or apoptosis has been a fascinating research topic in last 15 years since the reorganization that apoptosis is not only a physiological mechanism for cell homeostasis but also involved in pathological cell death in disease states such as in ischemic stroke, traumatic injury, infectious and degenerative diseases (Choi, 1996; Friedlander, 2003). Among the apoptotic pathways and signals discovered so far, excessive K⁺ efflux mediated by voltage-gated K⁺ channels and ligand-gated channels has emerged in recent years as a common pro-apoptotic event that lead to intracellular K⁺ depletion, cell volume decrease, caspase activation, cytochrome c release, DNA fragmentation, and apoptotic death (Mandegar & Yuan, 2002; Yu, 2003b; Lang et al., 2005). The K⁺ mechanism for apoptosis has been demonstrated in a wide variety of cell types including central neurons such as cortical, hippocampal, and cerebellar granule cells, and non-neuronal cells such as lymphocytes/thymocytes, vascular smooth muscle cells, and many cell lines (Yu, 2003b). It is clear that because of divergent channel expression patterns in different cells the routes that are capable of and involved in mediating pro-apoptotic K⁺ efflux are different. Many studies have identified voltage-gated Kv channels including delayed rectifier and A-type channels as major paths for massive K⁺ loss, but other K⁺ channels such as Ca²⁺- and ATP-dependent K⁺ channels as well as two-pore K⁺ channels may also play important roles. Accompanying the excessive K⁺ efflux via over-activated K⁺ channels, cells undergoing apoptosis ultimately suffer from dysfunction of Na⁺, K⁺-ATPase, which is considered an essential event in reducing intracellular K⁺ (Yu, 2003a).

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