Premium
Muscarinic Ca 2+ responses resistant to muscarinic antagonists at perisynaptic schwann cells of the frog neuromuscular junction
Author(s) -
Robitaille Richard,
Jahromi Babak S.,
Charlton Milton P.
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.337be.x
Subject(s) - muscarine , muscarinic acetylcholine receptor , oxotremorine , muscarinic acetylcholine receptor m1 , chemistry , muscarinic acetylcholine receptor m2 , acetylcholine , muscarinic acetylcholine receptor m3 , muscarinic agonist , muscarinic acetylcholine receptor m4 , muscarinic antagonist , atropine , endocrinology , muscarinic acetylcholine receptor m5 , pirenzepine , nicotinic agonist , medicine , pharmacology , biology , receptor , biochemistry
1 Acetylcholine causes a rise of intracellular Ca 2+ in perisynaptic Schwann cells (PSCs) of the frog neuromuscular junction. The signalling pathway was characterized using the fluorescent Ca 2+ indicator fluo‐3 and fluorescence microscopy. 2 Nicotinic antagonists had no effect on Ca 2+ responses evoked by ACh and no Ca 2+ responses were evoked with the nicotinic agonist nicotine. The muscarinic agonists muscarine and oxotremorine‐M induced Ca 2+ signals in PSCs. 3 Ca 2+ responses remained unchanged when extracellular Ca 2+ was removed, indicating that they are due to the release of Ca 2+ from internal stores. Incubation with pertussis toxin did not alter the Ca 2+ signals induced by muscarine, but did block depression of transmitter release induced by adenosine and prevented Ca 2+ responses in PSCs induced by adenosine. 4 The general muscarinic antagonists atropine, quinuclidinyl benzilate and N ‐methyl‐scopolamine failed to block Ca 2+ responses to muscarinic agonists. Atropine (at 20000‐fold excess concentration) also failed to reduce the proportion of cells responding to a threshold muscarine concentration sufficient to cause responses in less than 50% of cells. Only the allosteric, non‐specific blocker, gallamine (1–10 μ m ) was effective in blocking muscarine‐induced Ca 2+ responses. 5 In preparations denervated 7 days prior to experiments, low concentrations of atropine reversibly and completely blocked Ca 2+ responses to muscarine. 6 The lack of blockade by general muscarinic antagonists in innervated, in situ preparations suggests that muscarinic Ca 2+ responses at PSCs are not mediated by any of the five known muscarinic receptors or that post‐translational modification prevented antagonist binding.