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

Abstract

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 processes4,5, including activation of potassium channels through cGMP-dependent protein kinase6,7. 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 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.

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Bolotina, V., Najibi, S., Palacino, J. et al. Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature 368, 850–853 (1994). https://doi.org/10.1038/368850a0

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