| pubmed-article:12527722 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12527722 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:12527722 | lifeskim:mentions | umls-concept:C0013935 | lld:lifeskim |
| pubmed-article:12527722 | lifeskim:mentions | umls-concept:C0553257 | lld:lifeskim |
| pubmed-article:12527722 | lifeskim:mentions | umls-concept:C0026882 | lld:lifeskim |
| pubmed-article:12527722 | lifeskim:mentions | umls-concept:C1171362 | lld:lifeskim |
| pubmed-article:12527722 | lifeskim:mentions | umls-concept:C0006685 | lld:lifeskim |
| pubmed-article:12527722 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:12527722 | lifeskim:mentions | umls-concept:C0338484 | lld:lifeskim |
| pubmed-article:12527722 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:12527722 | lifeskim:mentions | umls-concept:C1515670 | lld:lifeskim |
| pubmed-article:12527722 | lifeskim:mentions | umls-concept:C0667268 | lld:lifeskim |
| pubmed-article:12527722 | lifeskim:mentions | umls-concept:C0392756 | lld:lifeskim |
| pubmed-article:12527722 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:12527722 | pubmed:issue | Pt 2 | lld:pubmed |
| pubmed-article:12527722 | pubmed:dateCreated | 2003-1-15 | lld:pubmed |
| pubmed-article:12527722 | pubmed:abstractText | Familial hemiplegic migraine is associated with at least 13 different missense mutations in the alpha1A Ca(2+) channel subunit. Some of these mutations have been shown to affect the biophysical properties of alpha1A currents. To date, no study has examined the influence of such mutations on the G-protein regulation of channel function. Because G-proteins inhibit movement of the voltage sensor, we examined the effects of the R192Q mutation, which neutralizes a positive charge in the first S4 segment. Human wild-type (WT) or R192Q mutant channels were expressed in human embryonic kidney tsA-201 cells along with dopamine D2 receptors. Application of quinpirole induced fast (approximately 1 s), pertussis toxin-sensitive inhibition of alpha1A(WT) and alpha1A(R192Q) Ca(2+) currents, consistent with the activation of a membrane-delimited pathway. alpha1A(WT) Ca(2+) currents were inhibited by 62.9 +/- 0.9 % (n = 27), whereas alpha1A(R192Q) Ca(2+) currents were inhibited by only 47.9 +/- 1.8 % (n = 35; P < 0.001). Concentration-response analysis showed that only the extent of inhibition was affected, with no change in agonist potency (EC(50) = 1 nM). Prepulse facilitation, which is a characteristic of voltage-dependent inhibition, was also reduced by the R192Q mutation. However, the kinetics of facilitation and slow activation were not affected, suggesting that G-protein-Ca(2+) channel affinity was unchanged. These results show that the R192Q mutation reduces the G-protein inhibition of P/Q-type Ca(2+) channels, probably by altering mechanisms by which Gbetagamma subunit binding induces a change in channel gating. Altered G-protein modulation and the consequent reduced presynaptic inhibition may contribute to migraine attacks by favouring a persistent state of hyperexcitability. | lld:pubmed |
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| pubmed-article:12527722 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12527722 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12527722 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12527722 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12527722 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:12527722 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12527722 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12527722 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:12527722 | pubmed:issn | 0022-3751 | lld:pubmed |
| pubmed-article:12527722 | pubmed:author | pubmed-author:GrabnerManfre... | lld:pubmed |
| pubmed-article:12527722 | pubmed:author | pubmed-author:SeabrookGuy... | lld:pubmed |
| pubmed-article:12527722 | pubmed:author | pubmed-author:MellitiKarimK | lld:pubmed |
| pubmed-article:12527722 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12527722 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:12527722 | pubmed:volume | 546 | lld:pubmed |
| pubmed-article:12527722 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12527722 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12527722 | pubmed:pagination | 337-47 | lld:pubmed |
| pubmed-article:12527722 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
| pubmed-article:12527722 | pubmed:meshHeading | pubmed-meshheading:12527722... | lld:pubmed |
| pubmed-article:12527722 | pubmed:meshHeading | pubmed-meshheading:12527722... | lld:pubmed |
