Review
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World J Biol Chem. May 26, 2014; 5(2): 85-92
Published online May 26, 2014. doi: 10.4331/wjbc.v5.i2.85
Oxidation of KCNB1 K+ channels in central nervous system and beyond
Federico Sesti, Xilong Wu, Shuang Liu
Federico Sesti, Xilong Wu, Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, United States
Shuang Liu, Department of Neurology, Jinan Central Hospital, Jinan 50013, Shandong Province, China
Author contributions: Sesti F and Wu X collected literature; Sesti F, Wu X and Liu S discussed the manuscript; Sesti F wrote the manuscript; Liu S prepared the figure.
Supported by National Science Foundation Grant to Sesti F, No. 1026958
Correspondence to: Federico Sesti, PhD, Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers University, RWJMS Research Building 683, Hoes Lane West Piscataway, Piscataway, NJ 08854, United States. federico.sesti@rutgers.edu
Telephone: +1-732-2354032 Fax: +1-732-2355038
Received: November 5, 2013
Revised: January 26, 2014
Accepted: March 3, 2014
Published online: May 26, 2014
Processing time: 218 Days and 9.4 Hours
Abstract

KCNB1, a voltage-gated potassium (K+) channel that conducts a major delayed rectifier current in the brain, pancreas and cardiovascular system is a key player in apoptotic programs associated with oxidative stress. As a result, this protein represents a bona fide drug target for limiting the toxic effects of oxygen radicals. Until recently the consensus view was that reactive oxygen species trigger a pro-apoptotic surge in KCNB1 current via phosphorylation and SNARE-dependent incorporation of KCNB1 channels into the plasma membrane. However, new evidence shows that KCNB1 can be modified by oxidants and that oxidized KCNB1 channels can directly activate pro-apoptotic signaling pathways. Hence, a more articulated picture of the pro-apoptotic role of KCNB1 is emerging in which the protein induces cell’s death through distinct molecular mechanisms and activation of multiple pathways. In this review article we discuss the diverse functional, toxic and protective roles that KCNB1 channels play in the major organs where they are expressed.

Keywords: Apoptosis; Kv2.1; Aging; Reactive oxygen species; Alzheimer’s disease

Core tip: KCNB1 is a K+ channel that plays a key role in the brain, pancreas and cardiovascular system. KCNB1 is unique in that it induces apoptosis in association with oxidative stress. In this review article we discuss the diverse roles of this channel in the organs where it is expressed including recent advances in the molecular mechanisms through which KCNB1 causes cytotoxicity.