NITRIC-OXIDE ACTIVATES MULTIPLE POTASSIUM CHANNELS IN CANINE COLONIC SMOOTH-MUSCLE

1. Nitric oxide (NO), an inhibitory neurotransmitter released from per ipheral neurones, hyperpolarizes smooth muscle cells and inhibits cont raction. The mechanism of this hyperpolarization is unknown. 2. We hav e identified three classes of K+ channels activated by NO and NO donor s 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-atta ched patches. 3. Dibutyryl cGMP and 8-bromo cGMP also increased the op en probability of K-NO1, and K-NO2, in cell-attached patches. 4. In ex cised 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 ha d no effect on the open probability of BK channels in excised patches. 5. The reducing agent dithiothreitol and the alkylating agent N-ethyl maleimide blocked NO-induced channel openings. 6. In summary, the hype rpolarization response to NO in smooth muscles may be mediated by mult iple K+ channels. At least two of these classes of channels may be act ivated by dual pathways involving direct activation by NO and cGMP-med iated mechanisms.