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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
1999-10-14
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pubmed:abstractText |
There are five known subtypes of muscarinic receptors (M(1)-M(5)). We have used knockout mice lacking the M(1), M(2), or M(4) receptors to determine which subtypes mediate modulation of voltage-gated Ca(2+) channels in mouse sympathetic neurons. Muscarinic agonists modulate N- and L-type Ca(2+) channels in these neurons through two distinct G-protein-mediated mechanisms. One pathway is fast and membrane-delimited and inhibits N- and P/Q-type channels by shifting their activation to more depolarized potentials. The other is slow and voltage-independent and uses a diffusible cytoplasmic messenger to inhibit both Ca(2+) channel types. Using patch-clamp methods on acutely dissociated sympathetic neurons, we isolated each pathway by pharmacological and kinetic means and found that each one is nearly absent in a particular knockout mouse. The fast and voltage-dependent pathway is lacking in the M(2) receptor knockout mice; the slow and voltage-independent pathway is absent from the M(1) receptor knockout mice; and neither pathway is affected in the M(4) receptor knockout mice. The knockout effects are clean and are apparently not accompanied by compensatory changes in other muscarinic receptors.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-10066893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-1316767,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-1321648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-1329101,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-1346090,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-1647174,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-1654413,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-1662279,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-1719369,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-1846449,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-1847065,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-1903186,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-1921982,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-2164405,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-2438697,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-2447647,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-2479736,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-2483099,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-2560643,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-2567963,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-2570354,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-6760380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-6965523,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-7506756,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-7516687,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-7525895,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-7532338,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-7678964,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-7768353,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-7932231,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-8014899,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-8410188,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-8637575,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-8637576,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-8893025,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9010213,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9037083,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9114253,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9121358,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9322468,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9371842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9481669,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9490860,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9501252,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9581771,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9614229,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9618554,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9687583,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9751781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10485923-9990086
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
96
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10899-904
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10485923-Animals,
pubmed-meshheading:10485923-Mice,
pubmed-meshheading:10485923-Time Factors,
pubmed-meshheading:10485923-Models, Biological,
pubmed-meshheading:10485923-Patch-Clamp Techniques,
pubmed-meshheading:10485923-Ethylmaleimide,
pubmed-meshheading:10485923-Oxotremorine,
pubmed-meshheading:10485923-Mice, Inbred C57BL,
pubmed-meshheading:10485923-Receptors, Muscarinic
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