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

Nature. 1994 Apr 28;368(6474):850-3. doi: 10.1038/368850a0.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Calcium / metabolism*
  • Cell Membrane / metabolism
  • Charybdotoxin
  • Cyclic GMP / metabolism
  • Ethylmaleimide / pharmacology
  • In Vitro Techniques
  • Magnesium / metabolism
  • Male
  • Membrane Potentials
  • Methylene Blue / pharmacology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Myristic Acid
  • Myristic Acids / pharmacology
  • Nitric Oxide / physiology*
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism*
  • Rabbits
  • Scorpion Venoms / pharmacology


  • Myristic Acids
  • Potassium Channels
  • Scorpion Venoms
  • Myristic Acid
  • Charybdotoxin
  • Nitric Oxide
  • Adenosine Triphosphate
  • Cyclic GMP
  • Magnesium
  • Ethylmaleimide
  • Calcium
  • Methylene Blue