Effect of KC399, a newly synthesized K⁺ channel opener, on acetylcholine‐induced electrical and mechanical activities in rabbit tracheal smooth muscle

Abstract

4 In O-escin-skinned strips, Ca2+ (0.3-10 gM) produced a contraction in a concentration-dependent manner. KC399 (0.1 gM) had no effect on the Ca2 -force relationship in the presence or absence of ATP with GTP. However, at a very high concentration (1 gM), this agent slightly shifted the relationship to the right and attenuated the maximum Ca2+-induced contraction. 5 We conclude that, in rabbit tracheal smooth muscle, the membrane hyperpolarization induced by KC399 attenuates the ACh-induced tonic increase in [Ca2+], through an inhibition of nicardipinesensitive and -insensitive Ca2'-influxes, thus causing an inhibition of the ACh-induced tonic contraction. The ACh-induced phasic increase in [Ca2+]i and force are also inhibited, but less effectively than the tonic ones, suggesting that the action of such K+ channel openers on agonist-induced responses may be slightly different in tracheal from vascular smooth muscle.

Effects of some K+‐channel inhibitors on the electrical behaviour of guinea‐pig isolated trachealis and on its responses to spasmogenic drugs

“…IbTX exhibits greater specificity for such channels (Galvez et al, 1990;Suarez-Kurtz et al, 1991). In canine trachealis muscle ChTX (100 nM) evoked depolarization in excess of 10 mV (Kamei et al, 1994). This finding may indicate that, in canine trachealis muscle, BKCa channels are open under resting conditions and help to determine the resting membrane potential.…”

“…This finding may indicate that, in canine trachealis muscle, BKCa channels are open under resting conditions and help to determine the resting membrane potential. However, the experiments of Kamei et al (1994) were not carried out in the presence of an atropine-like drug and it is therefore possible that the depolarizing effect of the toxin was a consequence of the toxin directly or indirectly activating muscarinic cholinoceptors on the smooth muscle cells. In the studies of Fleischmann et al (1993) (Murray et al, 1991;present study (Murray et al, 1989).…”

Regional and species differences in glyburide‐sensitive K+ channels in airway smooth muscles as estimated from actions of KC 128 and levcromakalim

“…administration of pentobarbitone (35 mg kg-') and exsanguinated. Segments of tracheal smooth muscle were prepared for all experiments as previously described (Kamei et al, 1994). Briefly, circular muscle strips were excised from the cervical part of the trachea and immediately placed in Krebs-Henseleit solution.…”

“…Concerning the K+ channel openers, the relaxant effect of these agents on carbachol-induced contraction is reported to be weaker in guinea-pig than in human preparations (Taylor et al, 1988;Imagawa et al, 1993). Recently, we have reported that in the dog tracheal smooth muscle tissues, the action of K+ channel openers shows greater similarity to human bronchi than to guinea-pig tracheal smooth muscle (Kamei et al, 1994).…”

Effects of ATP-sensitive potassium channel openers on the contractile and phosphatidylinositol responses of the rat trachea

“…However, since the K ATP channel seems not to be so important in airway smooth muscle, few studies, except for those of Challiss et al [4] and Kamei et al [5], have evaluated the effects of K ATP channel openers on the airway smooth muscle of bovines or dogs. These authors found that K ATP channel openers inhibited inositol phosphate or IP 3 accumulations.…”