Nitric oxide activates multiple potassium channels in canine colonic smooth muscle

1. Nitric oxide (NO), an inhibitory neurotransmitter released from peripheral neurones, hyperpolarizes smooth muscle cells and inhibits contraction. The mechanism of this hyperpolarization is unknown. 2. We have identified three classes of K+ channels activated by NO and NO donors in colonic smooth muscle cells. NO and NO donors increased the open probability of 80 pS channels (K-NO1), very small channels (< 4 pS, K-NO2), and 270 pS Ca2+-activated K+ channels (BK channels) in cell-attached patches. 3. Dibutyryl cGMP and 8-bromo cGMP also increased the open probability of K-NO1, and K-NO2, in cell-attached patches. 4. In excised patches of membrane, direct application of NO or the NO donor, S-nitroso-N-acetyl penicillamine (SNAP), increased the open probability of K-NO1 and K-NO2, but cGMP or dibutyryl cGMP had no effect. SNAP had no effect on the open probability of BK channels in excised patches. 5. The reducing agent dithiothreitol and the alkylating agent N-ethylmaleimide blocked NO-induced channel openings. 6. In summary, the hyperpolarization response to NO in smooth muscles may be mediated by multiple K+ channels. At least two of these classes of channels may be activated by dual pathways involving direct activation by NO and cGMP-mediated mechanisms.