Enzyme-linked oxygen sensing by potassium channels.
The ability of ion channels to respond to an acute perturbation in oxygen tension is a widespread phenomenon, which encompasses many of the major ion channel families. Integral to the ability of several ion channels to respond to acute hypoxic challenge is modulation by upstream enzymatic reactions, suggesting that many ion channels sense oxygen via enzyme-linked processes. Several enzyme-linked oxygen sensing systems have been proposed, including nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent production of hydrogen peroxide, hemoxygenase-dependent generation of carbon monoxide, adenosine monophosphate (AMP) kinase-dependent channel phosphorylation, and src-Lck protein tyrosine kinase, via a currently undetermined mechanism. Each of these enzymes has been shown to endow specific ion channels with the ability to respond to changes in oxygen, with hypoxia exclusively evoking channel inhibition. This article reviews these proposed mechanisms and presents new insights into how one system, hemeoxygenase-2, confers oxygen sensitivity to large conductance, voltage- and calcium-activated potassium channels.
School of Biosciences, Cardiff University, Cardiff, United Kingdom. kemp@cf.ac.uk
Paul J
PJ
Kemp
Vsevolod
V
Telezhkin
William J
WJ
Wilkinson
Ruth
R
Mears
Stuart B
SB
Hanmer
Hanne C
HC
Gadeberg
Carsten T
CT
Müller
Daniela
D
Riccardi
Stephen P
SP
Brazier
D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D019255:NADPH Oxidases / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
D015221:Potassium Channels; D019255:NADPH Oxidases; D019061:src-Family Kinases; D000263:Adenylate Kinase; D010100:Oxygen