Published online May 26, 2014. doi: 10.4331/wjbc.v5.i2.85
Revised: January 26, 2014
Accepted: March 3, 2014
Published online: May 26, 2014
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.
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.