Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle.
Nitric oxide is the major endothelium-derived relaxing factor (EDRF), 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, including activation of potassium channels through cGMP-dependent protein kinase. 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.
Bolotina
V M
VM
Robert Dawson Evans Department of Clinical Research, Boston University Medical Center, Massachusetts 02118.
Najibi
S
S
Palacino
J J
JJ
Pagano
P J
PJ
Cohen
R A
RA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D018999:Charybdotoxin; D006152:Cyclic GMP / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D008751:Methylene Blue / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D019814:Myristic Acid; D009227:Myristic Acids / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D012604:Scorpion Venoms / Q000494:pharmacology
D009227:Myristic Acids; D015221:Potassium Channels; D012604:Scorpion Venoms; D019814:Myristic Acid; D018999:Charybdotoxin; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D006152:Cyclic GMP; D008274:Magnesium; D005033:Ethylmaleimide; D002118:Calcium; D008751:Methylene Blue