Muscarinic receptors inhibit ATP-sensitive K+ channels in swine tracheal smooth muscle

Muscarinic receptors inhibit ATP-sensitive K+ channels in swine tracheal smooth muscle. Am. J. Physiol. 273 (Lung Cell. Mol. Physiol. 17): L478-L484, 1997.-The patch-clamp technique was used to characterize a cromakalim-induced current and its regulation by muscarinic receptors in tracheal smooth muscle cells. Cromakalim (10 mu M) activated a steady-state increase of 33-292 pA (91.2 +/- 8.8 pA, n = 43) in whole cell current, consistent with the activation of ATP-sensitive K+ (K-ATP) channels. Acetylcholine (10 nM-1 mu M), added cumulatively inhibited the cromakalim-induced current by 23.6 +/- 14.9 to 73.9 +/- 4.6%. This inhibition was blocked by pretreatment with atropine (1 mu M). The cromakalim-induced current was also inhibited 83.0 +/- 8.3% by phorbol 12-myristate 13-acetate (100 nM, n = 6). The inhibition of the cromakalim-induced current by acetylcholine (1 mu M) and phorbol 12-myristate 13-acetate (100 nM) was reduced to 27.3 +/- 3.1% (n = 10) and 32.8 +/- 7.8% (n = 3), respectively, in the presence of staurosporine (100 mu M). We conclude that muscarinic receptor stimulation inhibits K-ATP channel activity through the activation of protein kinase C. These findings suggest that K-ATP channels may play a role in the regulation of membrane potential and contractility in airway smooth muscle.