ATP Inhibits Smooth Muscle Ca2+-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 & 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_1 of 0.2-0.6 mM. Cromakalim, 10 μ M 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.