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EFFECTS OF BK Ca CHANNELS ON THE REDUCTION OF CYTOSOLIC Ca 2+ IN cGMP‐INDUCED RELAXATION OF GUINEAPIG TRACHEA
Author(s) -
Mikawa Kenichiro,
Kume Hiroaki,
Takagi Kenzo
Publication year - 1997
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1997.tb01804.x
Subject(s) - iberiotoxin , apamin , chemistry , medicine , endocrinology , atrial natriuretic peptide , trachealis muscle , charybdotoxin , inhibitory postsynaptic potential , glibenclamide , muscle relaxation , potassium channel , biophysics , biology , diabetes mellitus
SUMMARY 1. In order to examine the mechanisms of cGMP‐induced relaxation in airway smooth muscle, the effects of atrial natriuretic peptide (ANP) and 8‐brom cGMP on muscle tone were studied by measuring isometric tension, while the effects on cytosolic Ca 2+ concentrations were studied by measuring the spectra of fura‐2 loaded in guinea‐pig tracheal strips. 2. Atrial natriuretic peptide and 8‐brom cGMP caused a concentration‐dependent inhibition of spontaneous tone in the guinea‐pig trachea. The relaxant effects of these agents on spontaneous tone were markedly suppressed in the presence of iberiotoxin (IbTX), a selective inhibitor of large‐conductance Ca 2+ ‐activated K + (BKca) channels. Iberiotoxin (30 nmol/L) markedly affected the maximal effect induced by ANP and 8‐brom cGMP and augmented EC 70 values for ANP and EC 50 values for 8‐brom cGMP approximately 27‐ and 17‐fold, respectively. The inhibitory effects of IbTX on relaxation induced by these agents were diminished in the presence of 1 μmol/L nifedipine, an antagonist of voltage‐operated Ca 2+ channels (VOCC). 3. The inhibitory action of ANP and 8‐brom cGMP on spontaneous tone was not affected by the presence of 10 μmol/L glibenclamide, an inhibitor of ATP‐sensitive K + channels, and 100 nmol/L apamin, an inhibitor of small‐conductance Ca 2 +‐activated K + channels. When these agents were applied to tissues precontracted by high (40mmol/L) K + , the relaxant effects of these agents markedly diminished. 4. The extracellular Ca 2+ ‐dependent contraction was inhibited in the presence of 0.3 μmoI/L ANP or 0.1 mmol/L 8‐brom cGMP. Concentration—response curves to extracellular Ca 2+ (0.03—2.4 mmol/L) were markedly diminished by exposure to these agents. The maximal effect induced by extracellular Ca 2+ was affected by these agents. 5. Atrial natriuretic peptide caused an inhibition of spontaneous tone accompanied by a reduction in the intracellular Ca 2+ concentration. In the presence of IbTX, the elimination of both muscle tone and cytosolic Ca 2+ by ANP was suppressed. 6. We conclude that ANP and 8‐brom cGMP activate BKca channels and that the inhibition of Ca 2+ influx through VOCC, mediated by BKca channel activation, may be involved in cGMP‐dependent bronchodilation.