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

Abstract

1 A study has been made of the effects of inhibitors selective among plasmalemmal K+-channels on the sensitivity and responsiveness of guinea-pig trachealis muscle to carbachol, histamine and KCl. The effects of the K+-channel inhibitors on the resting membrane potential and spontaneous electrical activity of the trachealis cells have also been examined.

Inhibitory effects of large Ca2+-activated K+-channel blockers on β-adrenergic- and NO-donor-mediated relaxations of human and guinea-pig airway smooth muscles

“…However, it slightly increased the response to 3 × 10 -6 M ACh (EC 50-60 ) by approximately 10% as recently reported by Isaac et al (1996) for the response to carbachol. In addition, indomethacin pretreatment for 15 min reduced the basal tone by about 30%.…”

“…However, it has also been observed a slowly developing contraction in 60% of tissues with Ibtx (100 nM) (Templeton et al 1995) and a transient increase in some tissues with high concentrations of TEA (10 mM) (Black et al 1994). These data compare with those in guinea-pig trachea in which Ibtx but also Chtx induce stronger but also slowdevelopping spasms (Ibtx (100 nM): 83% of the maximal contraction to ACh after 60-min pretreatment and Chtx (100 nM): 15% after 20-min up to 53% after 60-min pretreatment) (Cook et al 1995;Isaac et al 1996). In addition, TEA evokes spasms corresponding to 15% and 60% maximal contraction to Ach, for a 5-min pretreatment with 1 mM and 8 mM concentrations, respectively (Foster et al 1983).…”

“…Recent findings suggest that BK Ca inhibition is mediated through muscarinic M 2 -receptor activation of inhibitory guanine nucleotide binding protein (Gi) (Kume and Kotlikoff 1991;Kume et al 1995). In addition, Ibtx and Chtx have been shown in guinea-pig trachea to potentiate the lower parts of the concentration-contraction curves to methacholine, up to a level of contraction near to 50-60% of maximal contraction to this muscarinic agonist (Isaac et al 1996). These results indirectly suggest that, at this level of contraction, BK Ca are at least in part inhibited by the muscarinic stimulation.…”

Second messengers, ion channels and pharmacology of airway smooth muscle

“…In addition, following stimulation with agents able to cause elevation of intracellular cyclic AMP levels, the high-conductance calciumsensitive potassium channel is activated: as mentioned above this is likely to be important in producing at least part of the relaxant response to b 2 -agonists [33±35]. ATPsensitive potassium channels (K ATP ) are also present in airway smooth muscle, although the lack of effectiveness of activators of K ATP such as levcromakalin or antagonists of K ATP such as glibenclamide in vivo on airway tone imply that K ATP is unlikely to be critically important in the regulation of contractile or relaxant responses in airway smooth muscle [77]. Recent molecular studies on the nature of the potassium channel subunits expressed in airway myocytes will help in defining the relative importance of these different channels [78,79].…”

Παράγοντες Που Επηρεάζουν Την Απελευθέρωση Του Μονοξειδίου Του Αζώτου (NO) Στους Αεραγωγούς

“…Οι Κ Ca θεωρούνται οι σημαντικότεροι στη ρύθμιση της αγωγιμότητας της μεμβράνης στα Κ + εξαιτίας της μεγάλης τους αγωγιμότητας, της ευαισθησίας τους στη συγκέντρωση των ιόντων ασβεστίου, της ευαισθησίας τους στο δυναμικό της μεμβράνης καθώς και του μεγάλου αριθμού τους στην κυτταρική μεμβράνη των ΛΜΙ. Οι Κ Ca είναι ασβέστιο-και τασεοεξαρτώμενοι και παίζουν σημαντικό ρόλο στην χάλαση των ΛΜΙ των αεραγωγών ανθρώπων και ζώων [62][63][64] .…”