MUSCARINIC RECEPTORS INHIBIT ATP-SENSITIVE K-MUSCLE( CHANNELS IN SWINE TRACHEAL SMOOTH)

Muscarinic receptors inhibit ATP-sensitive K+ channels in swine trache al smooth muscle. Am. J. Physiol. 273 (Lung Cell. Mol. Physiol. 17): L 478-L484, 1997.-The patch-clamp technique was used to characterize a c romakalim-induced current and its regulation by muscarinic receptors i n tracheal smooth muscle cells. Cromakalim (10 mu M) activated a stead y-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) ch annels. Acetylcholine (10 nM-1 mu M), added cumulatively inhibited the cromakalim-induced current by 23.6 +/- 14.9 to 73.9 +/- 4.6%. This in hibition was blocked by pretreatment with atropine (1 mu M). The croma kalim-induced current was also inhibited 83.0 +/- 8.3% by phorbol 12-m yristate 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 chann el activity through the activation of protein kinase C. These findings suggest that K-ATP channels may play a role in the regulation of memb rane potential and contractility in airway smooth muscle.