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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
1991-6-12
|
| pubmed:abstractText |
Recently we have shown that 4-aminopyridine (4-AP), a drug known to enhance transmitter release, stimulates the phosphorylation of the protein kinase C substrate B-50 (GAP-43) in rat brain synaptosomes and that this effect is dependent on the presence of extracellular Ca2+. Hence, we were interested in the relationship between changes induced by 4-AP in the intracellular free Ca2+ concentration ([Ca2+]i) and B-50 phosphorylation in synaptosomes. 4-AP (100 microM) elevates the [Ca2+]i (as determined with fura-2) to approximately the same extent as depolarization with 30 mM K+ (from an initial resting level of 240 nM to approximately 480 nM after treatment). However, the underlying mechanisms appear to be different: In the presence of 4-AP, depolarization with K+ still evoked an increase in [Ca2+]i, which was additive to the elevation caused by 4-AP. Several Ca2+ channel antagonists (CdCl2, LaCl3, and diphenylhydantoin) inhibited the increase in B-50 phosphorylation by 4-AP. It is interesting that the increase in [Ca2+]i and the increase in B-50 phosphorylation by 4-AP were attenuated by tetrodotoxin, a finding pointing to a possible involvement of Na+ channels in this action. These results suggest that 4-AP (indirectly) stimulates both Ca2+ influx and B-50 phosphorylation through voltage-dependent channels by a mechanism dependent on Na+ channel activity.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-Aminopyridine,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/GAP-43 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Channels
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0022-3042
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
56
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1827-35
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:1851203-4-Aminopyridine,
pubmed-meshheading:1851203-Animals,
pubmed-meshheading:1851203-Calcium,
pubmed-meshheading:1851203-Calcium Channels,
pubmed-meshheading:1851203-Electrochemistry,
pubmed-meshheading:1851203-GAP-43 Protein,
pubmed-meshheading:1851203-Intracellular Membranes,
pubmed-meshheading:1851203-Male,
pubmed-meshheading:1851203-Membrane Glycoproteins,
pubmed-meshheading:1851203-Nerve Tissue Proteins,
pubmed-meshheading:1851203-Osmolar Concentration,
pubmed-meshheading:1851203-Phosphatidylinositols,
pubmed-meshheading:1851203-Phosphoproteins,
pubmed-meshheading:1851203-Phosphorylation,
pubmed-meshheading:1851203-Rats,
pubmed-meshheading:1851203-Rats, Inbred Strains,
pubmed-meshheading:1851203-Sodium Channels,
pubmed-meshheading:1851203-Synapses,
pubmed-meshheading:1851203-Synaptosomes
|
| pubmed:year |
1991
|
| pubmed:articleTitle |
Presynaptic mechanism of action of 4-aminopyridine: changes in intracellular free Ca2+ concentration and its relationship to B-50 (GAP-43) phosphorylation.
|
| pubmed:affiliation |
Division of Molecular Neurobiology, Rudolf Magnus Institute, University of Utrecht, The Netherlands.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|