Calcium-activated potassium channels - a therapeutic target for modulating nitric oxide in cardiovascular disease?
BACKGROUND
Cardiovascular risk factors are often associated with endothelial dysfunction, which is also prognostic for occurrence of cardiovascular events. Endothelial dysfunction is reflected by blunted vasodilatation and reduced nitric oxide (NO) bioavailability. Endothelium-dependent vasodilatation is mediated by NO, prostacyclin, and an endothelium-derived hyperpolarising factor (EDHF), and involves small (SK) and intermediate (IK) conductance Ca(2+)-activated K(+) channels. Therefore, SK and IK channels may be drug targets for the treatment of endothelial dysfunction in cardiovascular disease.


METHODS
SK and IK channels are involved in EDHF-type vasodilatation, but recent studies suggest that these channels are also involved in the regulation of NO bioavailability. Here we review how SK and IK channels may regulate NO bioavailability.


RESULTS
Opening of SK and IK channels is associated with EDHF-type vasodilatation, but, through increased endothelial cell Ca(2+) influx, L-arginine uptake, and decreased ROS production, it may also lead to increased NO bioavailability and endothelium-dependent vasodilatation.


CONCLUSIONS
Opening of SK and IK channels can increase both EDHF and NO-mediated vasodilatation. Therefore, openers of SK and IK channels may have the potential of improving endothelial cell function in cardiovascular disease.
Dalsgaard
Thomas
T
Department of Pharmacology, Aarhus University, DK-8000 Aarhus C, Denmark. thomas.dalsgaard@farm.au.dk
Kroigaard
Christel
C
Simonsen
Ulf
U
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D051381:Rats; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D009569:Nitric Oxide