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Postsynaptic nicotinic receptor desensitized by non‐contractile Ca 2+ mobilization via protein kinase‐C activation at the mouse neuromuscular junction
Author(s) -
Kimura Ikuko,
Dezaki Katsuya,
Tsuneki Hiroshi,
Kimura Masayasu
Publication year - 1995
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.1476-5381.1995.tb13249.x
Subject(s) - medicine , endocrinology , staurosporine , chemistry , stimulation , muscle contraction , nicotinic agonist , contraction (grammar) , protein kinase c , receptor , biology , biochemistry , phosphorylation
1 Non‐contractile Ca 2+ mobilization (unaccompanied by muscle contraction) was initiated by nerve stimulation in the presence of neostigmine (more than 0.03 μ m ) at the endplate region of mouse diaphragm muscles. In the process of nicotinic receptor desensitization, the depressant effect of non‐contractile Ca 2+ on contractile Ca 2+ mobilization was investigated by measurement of Ca 2+ ‐aequorin luminescence. 2 When the phrenic nerve was stimulated with paired pulses having intervals of 150, 300, 600, 1000 and 2000 ms, contractile Ca 2+ transients were elicited during the generation of non‐contractile Ca 2+ mobilization. The amplitude of the contractile Ca 2+ transients elicited by the second pulse (S 2 ) was depressed at the shorter pulse intervals, but recovered to the initial contractile response (S 1 ) at longer pulse intervals. 3 The extent of depression of S 2 was enhanced by increasing the concentration of neostigmine (0.03 to 0.3 μ m ). When a low concentration (0.05 μ m ) of pancuronium, a competitive nicotinic antagonist, completely blocked non‐contractile Ca 2+ mobilization, the depression of S 2 was diminished. 4 The depression of S 2 was enhanced when the peak amplitude of non‐contractile Ca 2+ mobilization was raised by increasing the external Ca 2+ concentration from 1.3 to 5 m m . 5 Staurosporine (10 n m ), a protein kinase‐C inhibitor, diminished the depression of S 2 despite large amounts of non‐contractile Ca 2+ mobilization. The diminishing effect of staurosporine was counteracted by TPA (0.1 μ m ), a protein kinase‐C activator. 6 These findings suggest that non‐contractile Ca 2+ mobilization may enhance the desensitization of the postsynaptic nicotinic receptor via activation of protein kinase‐C at the neuromuscular junction.