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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1994-8-2
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pubmed:abstractText |
We studied, in rat sensory neurons, the modulation of high voltage-activated Ca2+ currents (ICa) mediated by the pertussis toxin-sensitive activation of muscarinic receptors, which were found to be of subtypes M2 or M4. Muscarine reversibly blocked somatic Ca2+ spikes but strong predepolarizations only partially relieved the inhibited Ca2+ current. On the other hand, the putative coupling messenger could not rapidly diffuse towards channels whose activity was recorded from a macro-patch. The perforated patch technique virtually prevented the response rundown present during whole-cell experiments. Both omega-conotoxin GVIA (omega-CgTx)-sensitive channels and omega-CgTx- and dihydropyridine-resistant channels are coupled to the muscarinic receptor, but not the L-channel. When measured in the same neuron, dose-response relationships for the first and subsequent agonist applications differed; maximal inhibition, the reciprocal of half-maximal concentration and the Hill coefficient were always highest in the first trial. Muscarine and oxotremorine exhibited monotone dose-response curves, but oxotremorine-M showed non-linear relationships which became monotonic when cells were intracellularly perfused with inhibitors of protein kinase A (PKA) and C (PKC), suggesting that either PKA or receptor-induced PKC could phosphorylate and thus inactive G-proteins or other unknown proteins involved in inhibitory muscarinic actions on ICa. In summary, these data provide a preliminary pharmacological characterization of the muscarinic inhibition of the Ca2+ channels in sensory neurons, with implications about agonist specificity and the interplay between signalling pathways.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Conus magus toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Mollusk Venoms,
http://linkedlifedata.com/resource/pubmed/chemical/Muscarine,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic,
http://linkedlifedata.com/resource/pubmed/chemical/omega-Conotoxins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0953-816X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
381-91
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8019675-Action Potentials,
pubmed-meshheading:8019675-Animals,
pubmed-meshheading:8019675-Calcium Channel Blockers,
pubmed-meshheading:8019675-Calcium Channels,
pubmed-meshheading:8019675-Electric Conductivity,
pubmed-meshheading:8019675-Kinetics,
pubmed-meshheading:8019675-Membrane Potentials,
pubmed-meshheading:8019675-Mollusk Venoms,
pubmed-meshheading:8019675-Muscarine,
pubmed-meshheading:8019675-Neurons, Afferent,
pubmed-meshheading:8019675-Peptides,
pubmed-meshheading:8019675-Protein Kinase Inhibitors,
pubmed-meshheading:8019675-Rats,
pubmed-meshheading:8019675-Rats, Sprague-Dawley,
pubmed-meshheading:8019675-Receptors, Muscarinic,
pubmed-meshheading:8019675-Signal Transduction,
pubmed-meshheading:8019675-omega-Conotoxins
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pubmed:year |
1994
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pubmed:articleTitle |
Muscarinic regulation of Ca2+ currents in rat sensory neurons: channel and receptor types, dose-response relationships and cross-talk pathways.
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pubmed:affiliation |
Department of General Physiology and Biochemistry, University of Milan, Italy.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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