FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1987922897> ?p ?o ?g. }

• W1987922897 endingPage "tw233" @default.
• W1987922897 startingPage "tw233" @default.
• W1987922897 abstract "Three distinct α 1 subunit genes encode T-type Ca 2+ channels (Ca V 3.1, Ca V 3.2, and Ca V 3.3), and these have nonredundant roles in pain transmission, cell proliferation, and cardiovascular function. Lysophosphatidic acid (LPA), a phospholipid involved in the development and growth of neurons, binds to members of a family of G protein-coupled receptors (GPCRs) called LPA1-5, of which LPA1 is the most abundant in the brain. LPA1 activates members of the Gα i , Gα q , and Gα 12/13 family of G proteins. Stimulated Gα 12/13 activates the Rho guanosine triphosphatase family member RhoA, which activates Rho-associated kinase (ROCK). ROCK isoforms phosphorylate (among other substrates) sodium and potassium channels. Previous studies have shown overlapping physiological responses to activation of either ROCK or T-type Ca 2+ channels, so Iftinca et al . investigated a role for ROCK in regulating T-type Ca 2+ channels. Whole-cell patch clamp assays on tsA-201 cells (a subclone of HEK 293 cells) transiently expressing rat Ca V 3.1 showed a dose-dependent decrease in channel current in response to LPA. Experiments with pertussis toxin (to block Gα i ) and protein kinase C inhibitors (to block signals downstream of Gα q ) suggested that the Gα 12/13 pathway mediated the inhibitory effect of LPA on Ca V 3.1 activity. Coexpression of dominant-negative mutants of Gα 12 and Gα 13 , or treatment with specific inhibitors of Rho or ROCK, substantially decreased the inhibitory effects of LPA. Mutation of Ser and Thr residues in putative ROCK-phosphorylation consensus sites (found between domains II and III) of Ca V 3.1 resulted in mutant channels that did not respond to LPA. These consensus sites are conserved in all T-type Ca 2+ channels, and the authors found that whereas LPA treatment also inhibited the activity of Ca V 3.3, it increased the activity of Ca V 3.2. The authors performed experiments in neurons isolated from the lateral habenula (LHb) nucleus (predominantly expressing Ca V 3.1) and the dorsal root ganglia (DRG, in which Ca V 3.2 is the major channel) of rats and found that the effects of LPA (decreasing currents in LHb neurons and increasing currents in the DRG) were all blocked by inhibition of ROCK. Together, these data describe a new mechanism of regulation of the activity of T-type Ca 2+ channels and, given that T-type Ca 2+ channels and ROCK are coexpressed in other cell types, suggest that this regulation might be important for various physiological processes. M. Iftinca, J. Hamid, L. Chen, D. Varela, R. Tadayonnejad, C. Altier, R. W. Turner, G. W. Zamponi, Regulation of T-type calcium channels by Rho-associated kinase. Nat. Neurosci. 10 , 854-860 (2007). [PubMed]" @default.
• W1987922897 created "2016-06-24" @default.
• W1987922897 creator A5040603302 @default.
• W1987922897 date "2007-06-27" @default.
• W1987922897 modified "2023-09-26" @default.
• W1987922897 title "Calcium Channels Get ROCKed" @default.
• W1987922897 doi "https://doi.org/10.1126/stke.3932007tw233" @default.
• W1987922897 hasPublicationYear "2007" @default.
• W1987922897 type Work @default.
• W1987922897 sameAs 1987922897 @default.
• W1987922897 citedByCount "0" @default.
• W1987922897 crossrefType "journal-article" @default.
• W1987922897 hasAuthorship W1987922897A5040603302 @default.
• W1987922897 hasConcept C135285700 @default.
• W1987922897 hasConcept C147944092 @default.
• W1987922897 hasConcept C153911025 @default.
• W1987922897 hasConcept C170493617 @default.
• W1987922897 hasConcept C174510640 @default.
• W1987922897 hasConcept C178790620 @default.
• W1987922897 hasConcept C184235292 @default.
• W1987922897 hasConcept C185592680 @default.
• W1987922897 hasConcept C18699975 @default.
• W1987922897 hasConcept C201800478 @default.
• W1987922897 hasConcept C2776661833 @default.
• W1987922897 hasConcept C2777093181 @default.
• W1987922897 hasConcept C49773422 @default.
• W1987922897 hasConcept C519063684 @default.
• W1987922897 hasConcept C55493867 @default.
• W1987922897 hasConcept C62478195 @default.
• W1987922897 hasConcept C80631254 @default.
• W1987922897 hasConcept C86803240 @default.
• W1987922897 hasConcept C95444343 @default.
• W1987922897 hasConceptScore W1987922897C135285700 @default.
• W1987922897 hasConceptScore W1987922897C147944092 @default.
• W1987922897 hasConceptScore W1987922897C153911025 @default.
• W1987922897 hasConceptScore W1987922897C170493617 @default.
• W1987922897 hasConceptScore W1987922897C174510640 @default.
• W1987922897 hasConceptScore W1987922897C178790620 @default.
• W1987922897 hasConceptScore W1987922897C184235292 @default.
• W1987922897 hasConceptScore W1987922897C185592680 @default.
• W1987922897 hasConceptScore W1987922897C18699975 @default.
• W1987922897 hasConceptScore W1987922897C201800478 @default.
• W1987922897 hasConceptScore W1987922897C2776661833 @default.
• W1987922897 hasConceptScore W1987922897C2777093181 @default.
• W1987922897 hasConceptScore W1987922897C49773422 @default.
• W1987922897 hasConceptScore W1987922897C519063684 @default.
• W1987922897 hasConceptScore W1987922897C55493867 @default.
• W1987922897 hasConceptScore W1987922897C62478195 @default.
• W1987922897 hasConceptScore W1987922897C80631254 @default.
• W1987922897 hasConceptScore W1987922897C86803240 @default.
• W1987922897 hasConceptScore W1987922897C95444343 @default.
• W1987922897 hasIssue "393" @default.
• W1987922897 hasLocation W19879228971 @default.
• W1987922897 hasOpenAccess W1987922897 @default.
• W1987922897 hasPrimaryLocation W19879228971 @default.
• W1987922897 hasRelatedWork W1994711691 @default.
• W1987922897 hasRelatedWork W2004824042 @default.
• W1987922897 hasRelatedWork W2011881892 @default.
• W1987922897 hasRelatedWork W2162625483 @default.
• W1987922897 hasRelatedWork W2181260782 @default.
• W1987922897 hasRelatedWork W2346048935 @default.
• W1987922897 hasRelatedWork W2748952813 @default.
• W1987922897 hasRelatedWork W2899084033 @default.
• W1987922897 hasRelatedWork W3136415254 @default.
• W1987922897 hasRelatedWork W4285097785 @default.
• W1987922897 hasVolume "2007" @default.
• W1987922897 isParatext "false" @default.
• W1987922897 isRetracted "false" @default.
• W1987922897 magId "1987922897" @default.
• W1987922897 workType "article" @default.