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 & Weston 1990). A K$^{+}$ channel, which is uniquely sensitive to cytoplasmic ATP (K$_{\text{ATP}}$), 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 Ca$^{2+}$-sensitive channel, otherwise indistinguishable from the large-conductance Ca$^{2+}$-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$_{\text{o}}$) of rabbit aortic, rabbit tracheal and pig coronary artery BK channels with a K$_1$ of 0.2-0.6 mM. Cromakalim, 10 $\mu $M partially reversed the ATP induced inhibition and increased P$_{\text{o}}$. Our observations raise the possibility that the ubiquitous BK channel may play a role during pathophysiological events.