ATP INHIBITS SMOOTH-MUSCLE CA-2+-ACTIVATED K+ CHANNELS

There has been much recent interest in the roles played by smooth-muscle K+ channels in protecting cells against ischemic and anoxic insults and in therapeutic vaso- and bronchodilation (Buckingham 1990; Longmore and Weston 1990). A K+ channel, which is uniquely sensitive to cytoplasmic ATP (K(ATP)), has been identified as a likely candidate for mediating these important functions (Standen et al. 1989). We now show, by using electrophysiological techniques in three different types of smooth muscle, that a large-conductance voltage and Ca2+-sensitive channel, otherwise indistinguishable from the large-conductance Ca2+-activated K+ channel (BK channel), is also sensitive to cytoplasmic ATP and cromakalim. ATP, in a dose-dependent manner, decreased the probability of channel opening (P(o) of rabbit aortic, rabbit tracheal and pig coronary artery BK channels with a K(i) of 0.2-0.6 mM. Cromakalim, 10 μM, partially reversed the ATP induced inhibition and increased P(o). Our observations raise the possibility that the ubiquitous BK channel may play a role during pathophysiological events.