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Effect of membrane hyperpolarization induced by a K + channel opener on histamine‐induced Ca 2+ mobilization in rabbit arterial smooth muscle
Author(s) -
Watanabe Yoshimasa,
Suzuki Akito,
Suzuki Hikaru,
Itoh Takeo
Publication year - 1996
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.1476-5381.1996.tb16729.x
Subject(s) - hyperpolarization (physics) , depolarization , chemistry , glibenclamide , histamine , membrane potential , biophysics , ryanodine receptor , medicine , endocrinology , tonic (physiology) , agonist , intracellular , biochemistry , stereochemistry , receptor , biology , nuclear magnetic resonance spectroscopy , diabetes mellitus
1 The role of membrane hyperpolarization on agonist‐induced contraction was investigated in intact and α‐toxin‐skinned smooth muscles of rabbit mesenteric artery by use of the ATP‐sensitive K + channel opener, (−)‐(3S,4R)‐4‐(N‐acetyl‐N‐hydroxyamino)‐6‐cyano‐3,4‐dihydro‐2,2‐dimethyl‐2H‐1‐benzopyran‐3‐01 (Y‐26763), and either histamine (Hist) or noradrenaline (NA). 2 Hist (3 μ m ) and NA (10 μ m ) both produced a phasic, followed by a tonic increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) and force. Y‐26763 (10 μ m ) potently inhibited the NA‐induced phasic and tonic increase in [Ca 2+ ] i and force. In contrast, Y‐26763 attenuated the Hist‐induced phasic increase in [Ca 2+ ] i and force but had almost no effect on the tonic response. However, ryanodine‐treatment of muscles in order to inhibit the function of intracellular Ca 2+ storage sites altered the action of Y‐26763 which now attenuated the Hist‐induced tonic increase in [Ca 2+ ] i and force in a concentration‐dependent manner (at concentrations > 1 μ m ). Glibenclamide (10 μ m ) attenuated the inhibitory action of Y‐26763. 3 Hist (3 μ m ) depolarized the smooth muscle cells to the same extent as NA (10 μ m ). In the absence of either agonist, Y‐26763 (over 30 nM) hyperpolarized the membrane and glibenclamide inhibited this hyperpolarization. Y‐26763 (10 μ m ) almost abolished the NA‐induced membrane depolarization, but only slightly attenuated the Hist‐induced membrane depolarization in which the delta (Δ) value (the difference before and after application of Hist) was not modified by any concentration of Y‐26763. In ryanodine‐treated smooth muscle cells, Y‐26763 hyperpolarized the membrane and potently inhibited the membrane depolarization induced by Hist. 4 In ryanodine‐treated muscle, Y‐26763 had no measurable effect on the Hist‐induced [Ca 2+ ] i ‐force relationship. Y‐26763 also had no apparent effect on the myofilament Ca 2+ ‐sensitivity in the presence of Hist in α‐toxin‐skinned smooth muscles. 5 It is concluded that the membrane hyperpolarization induced by Y‐26763 may not be enough to inhibit the Hist‐activated Ca 2+ influx. It is also suggested that Hist prevents the membrane hyperpolarization induced by Y‐26763, activating an unknown mechanism which is thought to depend on the function of intracellular Ca 2+ storage sites.