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Inhibition of transmitter release from rat sympathetic neurons via presynaptic M 1 muscarinic acetylcholine receptors
Author(s) -
Kubista H,
Kosenburger K,
Mahlknecht P,
Drobny H,
Boehm S
Publication year - 2009
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.1476-5381.2009.00136.x
Subject(s) - oxotremorine , muscarinic acetylcholine receptor , pertussis toxin , receptor , superior cervical ganglion , agonist , acetylcholine , endocrinology , inhibitory postsynaptic potential , chemistry , muscarinic acetylcholine receptor m2 , medicine , biology , g protein
Background and purpose: M 2 , M 3 and/or M 4 muscarinic acetylcholine receptors have been reported to mediate presynaptic inhibition in sympathetic neurons. M 1 receptors mediate an inhibition of K v 7, Ca V 1 and Ca V 2.2 channels. These effects cause increases and decreases in transmitter release, respectively, but presynaptic M 1 receptors are generally considered facilitatory. Here, we searched for inhibitory presynaptic M 1 receptors. Experimental approach: In primary cultures of rat superior cervical ganglion neurons, Ca 2+ currents were recorded via the perforated patch‐clamp technique, and the release of [ 3 H]‐noradrenaline was determined. Key results: The muscarinic agonist oxotremorine M (OxoM) transiently enhanced 3 H outflow and reduced electrically evoked release, once the stimulant effect had faded. The stimulant effect was enhanced by pertussis toxin (PTX) and was abolished by blocking M 1 receptors, by opening K v 7 channels and by preventing action potential propagation. The inhibitory effect was not altered by preventing action potentials or by opening K v 7 channels, but was reduced by PTX and ω‐conotoxin GVIA. The inhibition remaining after PTX treatment was abolished by blockage of M 1 receptors or inhibition of phospholipase C. When [ 3 H]‐noradrenaline release was triggered independently of voltage‐activated Ca 2+ channels (VACCs), OxoM failed to cause any inhibition. The inhibition of Ca 2+ currents by OxoM was also reduced by ω‐conotoxin and PTX and was abolished by M 1 antagonism in PTX‐treated neurons. Conclusions and implications: These results demonstrate that M 1 , in addition to M 2 , M 3 and M 4 , receptors mediate presynaptic inhibition in sympathetic neurons using phospholipase C to close VACCs.