Linked Life Data

20484531

Source:http://linkedlifedata.com/resource/pubmed/id/20484531

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-7-8
pubmed:abstractText
Familial hemiplegic migraine type-1 FHM-1 is caused by missense mutations in the CACNA1A gene that encodes the alpha(1A) pore-forming subunit of Ca(V)2.1 Ca(2+) channels. We used knock-in (KI) transgenic mice harboring the pathogenic FHM-1 mutation R192Q to study neurotransmission at the calyx of Held synapse and cortical layer 2/3 pyramidal cells (PCs). Using whole cell patch-clamp recordings in brain stem slices, we confirmed that KI Ca(V)2.1 Ca(2+) channels activated at more hyperpolarizing potentials. However, calyceal presynaptic calcium currents (I(pCa)) evoked by presynaptic action potentials (APs) were similar in amplitude, kinetic parameters, and neurotransmitter release. Ca(V)2.1 Ca(2+) channels in cortical layer 2/3 PCs from KI mice also showed a negative shift in their activation voltage. PCs had APs with longer durations and smaller amplitudes than the calyx of Held. AP-evoked Ca(2+) currents (I(Ca)) from PCs were larger in KI compared with wild-type (WT) mice. In contrast, when I(Ca)was evoked in PCs by calyx of Held AP waveforms, we observed no amplitude differences between WT and KI mice. In the same way, Ca(2+) currents evoked at the presynaptic terminals (I(pCa))of the calyx of Held by the AP waveforms of the PCs had larger amplitudes in R192Q KI mice that in WT. These results suggest that longer time courses of pyramidal APs were a key factor for the expression of a synaptic gain of function in the KI mice. In addition, our results indicate that consequences of FHM-1 mutations might vary according to the shape of APs in charge of triggering synaptic transmission (neurons in the calyx of Held vs. excitatory/inhibitory neurons in the cortex), adding to the complexity of the pathophysiology of migraine.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-10024348, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-10212483, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-10627581, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-10734061, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-12235360, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-12486151, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-12628170, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-15003170, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-15548652, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-15699344, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-15743764, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-15795222, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-15820400, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-15843616, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-16111830, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-16723526, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-17093120, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-17234697, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-17823210, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-18034688, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-18057200, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-18832426, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-19285472, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-20010820, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-7837096, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-7908596, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-9488686, http://linkedlifedata.com/resource/pubmed/commentcorrection/20484531-9575291
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1522-1598
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
291-9
pubmed:dateRevised
2011-8-1
pubmed:meshHeading
pubmed-meshheading:20484531-Action Potentials, pubmed-meshheading:20484531-Animals, pubmed-meshheading:20484531-Calcium Channels, pubmed-meshheading:20484531-Cerebral Cortex, pubmed-meshheading:20484531-Electric Stimulation, pubmed-meshheading:20484531-Electrophysiological Phenomena, pubmed-meshheading:20484531-Excitatory Postsynaptic Potentials, pubmed-meshheading:20484531-Humans, pubmed-meshheading:20484531-Mice, pubmed-meshheading:20484531-Mice, Inbred C57BL, pubmed-meshheading:20484531-Mice, Transgenic, pubmed-meshheading:20484531-Migraine Disorders, pubmed-meshheading:20484531-Migraine with Aura, pubmed-meshheading:20484531-Neurons, Afferent, pubmed-meshheading:20484531-Neurotransmitter Agents, pubmed-meshheading:20484531-Patch-Clamp Techniques, pubmed-meshheading:20484531-Pyramidal Cells, pubmed-meshheading:20484531-Synapses, pubmed-meshheading:20484531-Synaptic Transmission
pubmed:year
2010
pubmed:articleTitle
Gain of function in FHM-1 Ca(V)2.1 knock-in mice is related to the shape of the action potential.
pubmed:affiliation
Instituto de Fisiología, Biología Molecular y Neurociencias, Consejo Nacional de Investigaciones Científicas y Técnicas, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't