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-de
pendent modification of several intracellular processes(4-5), includin
g activation of potassium channels through cGMP-dependent protein kina
se(6,7). Here we present evidence that both exogenous nitric oxide and
native EDRF can directly activate single Ca2+-dependent K+ channels (
K-Ca(+)) in cell-free membrane patches without requiring cGMP. Under c
onditions when guanylate cyclase was inhibited by methylene blue, cons
iderable relaxation of rabbit aorta to nitric oxide persisted which wa
s blocked by charybdotoxin, a specific inhibitor of K-Ca(+) channels.
These studies demonstrate a novel direct action of nitric oxide on K-C
a(+) channels.