REGIONAL-DIFFERENCES AND SPECIES-DIFFERENCES IN GLYBURIDE-SENSITIVE K-128 AND LEVCROMAKALIM( CHANNELS IN AIRWAY SMOOTH MUSCLES AS ESTIMATEDFROM ACTIONS OF KC)

1 The purpose of the present experiments was to elucidate the differen ces in actions of two K+ channel openers, KC 128 and levcromakalim, on the carbachol-induced contraction, membrane potential and Rb-86(+) ef flux of the dog tracheal and bronchial smooth muscles. Furthermore, we compared the effects of these agents on guinea-pig and human airway s mooth muscles. 2 In the dog tracheal and bronchial smooth muscle tissu es, levcromakalim induced a concentration-dependent relaxation of the carbachol-induced contraction. The IC50 values were 0.35 mu M (IC50: 6 .46 +/- 0.10, n = 9) and 0.55 mu M (pIC(50): 6.26 +/- 0.07, n = 5), re spectively. KC 128 relaxed bronchial smooth muscles precontracted by c arbachol with an IC50 value of 0.19 mu M (pIC(50): 6.73 +/- 0.10, n = 7). However, KC 128 had almost no effect on the contraction evoked by carbachol in the trachea (IC50> 10 mu M) The relaxations induced by le vcromakalim and KC 128 were antagonized by glyburide (0.03-1 mu M) but not by charybdotoxin (100 nM). 3 Levcromakalim (1 mu M) hyperpolarize d the membrane of both dog tracheal and bronchial smooth muscle cells, whereas KC 128 (1 mu M) hyperpolarized the membrane of bronchial but not of tracheal smooth muscle cells. 4 Levcromakalim (10 mu M) increas ed Rb-86(+) efflux rate from both tracheal and bronchial smooth muscle tissues but KC 128 (10 mu M) increased Rb-86(+) efflux rate only from bronchial and not tracheal smooth muscle tissues. Glyburide (1 mu M) prevented the hyperpolarization and the Rb-86(+) efflux induced by the se agents at the same concentration as observed for mechanical respons es. 5 Both KC 128 and levcromakalim relaxed the guinea-pig isolated tr acheal smooth muscles precontracted by carbachol (100 nM), histamine ( 3 mu M) or U46619 (10 nM). KC 128 was approximately 10 times more pote nt than levcromakalim for each agonist. 6 In human bronchial smooth mu scles, levcromakalim but not KC 128 induced a concentration-dependent relaxation of the carbachol-induced contraction. 7 It is concluded tha t KC 128 has relaxant and hyperpolarizing effects in the dog bronchial and guinea-pig tracheal smooth muscles, but not in the dog tracheal a nd human bronchial smooth muscles. On the other hand, levcromakalim ac ts consistently on all the above airway smooth muscle tissues. These r esults indicate that there are regional and species differences in dis tribution of K+ channels, and at least two different K+ channel opener - and glyburide-sensitive K+ channels are present in the dog airway sm ooth muscles.