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The properties of ryanodine‐sensitive Ca 2+ release in mouse gastric smooth muscle cells
Author(s) -
Tokutomi Yoshiko,
Tokutomi Naofumi,
Nishi Katsuhide
Publication year - 2001
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 - 10.1038/sj.bjp.0704048
Subject(s) - caffeine , ryanodine receptor , chemistry , carbachol , tetraethylammonium , apamin , contraction (grammar) , iberiotoxin , muscle contraction , endocrinology , muscle relaxation , medicine , biophysics , charybdotoxin , calcium , intracellular , membrane potential , biochemistry , potassium , biology , receptor , organic chemistry
Under voltage‐clamped conditions, gastric smooth muscle cells of BALB/c mice developed spontaneous (STOCs) and caffeine‐ ( I CAF ) and carbachol‐induced ( I CCh ) transient outward currents. In fura‐2 microscopic measurements of intracellular Ca 2+ concentration ([Ca 2+ ] i ), caffeine and carbachol (CCh) provoked similar transient [Ca 2+ ] i elevations. Both I CCh and CCh‐induced [Ca 2+ ] i elevation of single smooth muscle cells occurred in an ‘all‐or‐nothing’ fashion in contrast to the reproducible caffeine responses. On the basis of the suppression of STOCs and I CAF by nicardipine, tetraethylammonium and iberiotoxin, but not by charybdotoxin nor apamin, it was suggested that both currents were generated by large conductance type Ca 2+ ‐activated K + channels. In measurements of isometric tension, caffeine produced relaxation of gastric smooth muscle strips in a concentration‐dependent manner (0.1 – 3 m M ). The concentration‐dependent relaxation with caffeine was mimicked by dibutyryl cyclic AMP which produced potentiation of contraction triggered by 50 m M KCl. At caffeine concentrations >3 m M , a transient contraction followed by relaxation was provoked as the quasi maximal response to caffeine. In the quasi maximal response, caffeine acted as a potent relaxant in smooth muscle strips precontracted with 50 m M KCl or 3 μ M CCh. The relaxation with caffeine was significantly accelerated in those strips precontracted with KCl or CCh. All these results suggest that ryanodine‐sensitive Ca 2+ release, which is triggered by caffeine, is an important modifier of Ca 2+ homeostasis in the cytoplasm and the contractility of gastric smooth muscle cells of mice.British Journal of Pharmacology (2001) 133 , 125–137; doi: 10.1038/sj.bjp.0704048