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Tetrodotoxin‐sensitive, K + ‐induced relaxation of guinea‐pig isolated trachealis in the presence of Ca 2+ ‐entry blocking drugs, Ca 2+ ‐free solution and after polyamine exposure
Author(s) -
Chideckel Elliott W.,
Fedan Jeffrey S.,
Mike Pamela
Publication year - 1986
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.1476-5381.1986.tb11117.x
Subject(s) - trachealis muscle , chemistry , ouabain , tetrodotoxin , verapamil , nifedipine , propranolol , biophysics , tetraethylammonium , calcium , endocrinology , membrane potential , potassium , sodium , biochemistry , charybdotoxin , medicine , biology , organic chemistry
1 We have previously observed a paradoxical relaxant effect of K + on guinea‐pig isolated trachealis after exposure to polyamines. The purpose of the present study was to evaluate whether the relaxation involved a reduction in the entry of extracellular Ca 2+ . We therefore investigated the effect of K + in the presence of Ca 2+ ‐entry blocking drugs and in the presence of Ca 2+ ‐free solution. 2 In the presence of nifedipine (10 −5 M), verapamil (10 −5 M) or diltiazem (10 −5 M), K + (30 mM) induced relaxation of the trachealis muscle. The relaxation to K + was not blocked by ouabain (10 −6 M), propranolol (10 −6 M), or indomethacin (10 −6 M). 3 A relaxation in response to K + was also observed in Ca 2+ ‐free solution, (with tone induced by methacholine), an effect not blocked by propranolol or ouabain. 4 Tetraethylammonium (30 mM) (TEA), which ordinarily evokes contractile responses, induced trachealis relaxation in the presence of verapamil or nifedipine. The relaxation was unaltered by ouabain or propranolol. 5 Tetrodotoxin (10 −6 M) (TTX) blocked 65% of the K + ‐induced relaxation in the presence of nifedipine and 100% of K + ‐induced relaxation either in a Ca 2+ ‐free solution or after polyamine exposure. TTX was without effect on TEA‐induced relaxation after Ca 2+ ‐entry blocking drugs. 6 Atropine (10 −6 M) or hexamethonium (10 −6 M) did not affect K + ‐induced relaxation after polyamine exposure. 7 The concentration‐response curve for K + ‐induced contraction in normal modified Krebs‐Henseleit solution was shifted to the left by TTX. 8 It is concluded: (a) K + has a direct effect on the trachealis causing contraction and an indirect effect, mediated by neurotransmitter release, causing relaxation. This latter effect is exposed when the direct effect is inhibited by Ca 2+ ‐entry blocking drugs, Ca 2+ ‐free solution or polyamine exposure; the indirect effect is non‐adrenergic, non‐cholinergic and not via ganglionic transmission; (b) the TEA‐induced relaxation and a component of the K + ‐induced relaxation after Ca 2+ blocking drugs cannot be explained by neurotransmitter release; (c) polyamines may act as naturally occurring Ca 2+ antagonists.