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Guinea‐pig isolated trachealis: the effects of charybdotoxin on mechanical activity, membrane potential changes and the activity of plasmalemmal K + ‐channels
Author(s) -
Murray M.A.,
Berry J.L.,
Cook S.J.,
Foster R.W.,
Green K.A.,
Small R.C.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb09868.x
Subject(s) - charybdotoxin , trachealis muscle , chemistry , biophysics , isoprenaline , guinea pig , electrophysiology , cromakalim , membrane potential , potassium channel , biochemistry , medicine , endocrinology , biology , receptor , stimulation , agonist
1 A study has been made, in guinea‐pig isolated trachealis, of the effects of charybdotoxin in modulating (a) the activity of large conductance K + ‐channels, (b) the spontaneous electrical activity of intact cells and (c) the mechanical effects of some bronchodilator drugs. 2 Single smooth muscle cells were isolated from guinea‐pig trachealis by enzymic digestion and were studied by the patch clamp recording technique. Recordings were made from outside‐out plasmalemmal patches when the medium bathing the external surface of the patches contained 1.2 m m Ca 2+ and 6 m m K + while that bathing the cytosolic surface contained 0.1 μ m Ca 2+ and 140 m m K + . Charybdotoxin (100 n m ), applied to the external surface of patches held at 0 mV, abolished the unitary currents associated with the opening of large conductance K + ‐channels. 3 Opened segments of guinea‐pig trachea were used for the simultaneous recording of membrane potential and tension changes. In these experiments charybdotoxin (100 n m ) caused the conversion of spontaneous electrical slow waves into spike‐like action potentials. This effect was accompanied by a very small reduction in resting membrane potential. 4 Tissue bath recording showed that charybdotoxin (100 n m ) increased the spontaneous mechanical tone of the tissue, antagonized (2.8 fold in each case) the relaxant actions of isoprenaline and theophylline but did not antagonize the relaxant actions of cromakalim or RP 49356. 5 It is concluded that charybdotoxin is an effective inhibitor of large conductance K + ‐channels in guinea‐pig trachealis cells. The ability of charybdotoxin to convert spontaneous slow waves into spike‐like action potentials suggests that the large, charybdotoxin‐sensitive, K + ‐channels play an important role in determining the strong outward rectifying behaviour of the cells. The ability of charybdotoxin to antagonize isoprenaline and theophylline, but not to antagonize cromakalim and RP 49356, suggests that opening of the large conductance, charybdotoxin‐sensitive K + ‐channel is implicated in the action of the former but not the latter pair of bronchodilator drugs.