Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle

NITRIC oxide is the major endothelium-derived relaxing factor (EDRF) 1–3 , and it is thought to relax smooth muscle cells by stimulation of guanylate cyclase, accumulation of its product cyclic GMP, and cGMP-dependent modification of several intracellular processes 4,5 , including activation of pota...

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Bibliographic Details
Published in:Nature (London) 1994-04, Vol.368 (6474), p.850-853
Main Authors: Bolotina, Victoria M, Najibi, Soheil, Palacino, James J, Pagano, Patrick J, Cohen, Richard A
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Animals
Biological and medical sciences
Blood vessels and receptors
Calcium
Calcium - metabolism
Cell Membrane - metabolism
Cellular biology
Charybdotoxin
Cyclic GMP - metabolism
Ethylmaleimide - pharmacology
Fundamental and applied biological sciences. Psychology
Humanities and Social Sciences
In Vitro Techniques
letter
Magnesium - metabolism
Male
Membrane Potentials
Methylene Blue - pharmacology
multidisciplinary
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - metabolism
Muscular system
Myristic Acid
Myristic Acids - pharmacology
Nitric oxide
Nitric Oxide - physiology
Potassium Channels - drug effects
Potassium Channels - metabolism
Rabbits
Science
Science (multidisciplinary)
Scorpion Venoms - pharmacology
Vertebrates: cardiovascular system
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Summary:NITRIC oxide is the major endothelium-derived relaxing factor (EDRF) 1–3 , and it is thought to relax smooth muscle cells by stimulation of guanylate cyclase, accumulation of its product cyclic GMP, and cGMP-dependent modification of several intracellular processes 4,5 , including activation of potassium channels through cGMP-dependent protein kinase 6,7 . Here we present evidence that both exogenous nitric oxide and native EDRF can directly activate single Ca 2+ -dependent K + channels (K + Ca ) in cell-free membrane patches without requiring cGMP. Under conditions when guanylate cyclase was inhibited by methylene blue, considerable relaxation of rabbit aorta to nitric oxide persisted which was blocked by charybdotoxin, a specific inhibitor of K + Ca channels. These studies demonstrate a novel direct action of nitric oxide on K + Ca channels.
ISSN:0028-0836
1476-4687
DOI:10.1038/368850a0