Matches in SemOpenAlex for { <https://semopenalex.org/work/W2582148964> ?p ?o ?g. }
- W2582148964 endingPage "2477" @default.
- W2582148964 startingPage "2465" @default.
- W2582148964 abstract "Key points Cav1.2 channels maintain activity through interactions with calmodulin (CaM). In this study, activities of the Cav1.2 channel (α1C) and of mutant‐derivatives, C‐terminal deleted (α1CΔ) and α1CΔ linked with CaM (α1CΔCaM), were compared in the inside‐out mode. α1CΔ with CaM, but not without CaM, and α1CΔCaM were active, suggesting that CaM induced channel activity through a dynamic interaction with the channel, even without the distal C‐tail. ATP induced α1C activity with CaM and enhanced activity of the mutant channels. Okadaic acid mimicked the effect of ATP on the wildtype but not mutant channels. These results supported the hypothesis that CaM and ATP maintain activity of Cav1.2 channels through their dynamic interactions. ATP effects involve mechanisms both related and unrelated to channel phosphorylation. CaM‐linked channels are useful tools for investigating Cav1.2 channels in the inside‐out mode; the fast run‐down is prevented by only ATP and the slow run‐down is nearly absent. Abstract Calmodulin (CaM) plays a critical role in regulation of Cav1.2 Ca 2+ channels. CaM binds to the channel directly, maintaining channel activity and regulating it in a Ca 2+ ‐dependent manner. To explore the molecular mechanisms involved, we compared the activity of the wildtype channel (α1C) and mutant derivatives, C‐terminal deleted (α1C∆) and α1C∆ linked to CaM (α1C∆CaM). These were co‐expressed with β2a and α2δ subunits in HEK293 cells. In the inside‐out mode, α1C and α1C∆ showed minimal open‐probabilities in a basic internal solution (run‐down), whereas α1C∆ with CaM and α1C∆CaM maintained detectable channel activity, confirming that CaM was necessary, but not sufficient, for channel activity. Previously, we reported that ATP was required to maintain channel activity of α1C. Unlike α1C, the mutant channels did not require ATP for activation in the early phase (3–5 min). However, α1C∆ with CaM + ATP and α1C∆CaM with ATP maintained activity, even in the late phase (after 7–9 min). These results suggested that CaM and ATP interacted dynamically with the proximal C‐terminal tail of the channel and, thereby, produced channel activity. In addition, okadaic acid, a protein phosphatase inhibitor, could substitute for the effects of ATP on α1C but not on the mutant channels. These results supported the hypothesis that CaM and ATP maintain activity of Cav1.2 channels, further indicating that ATP has dual effects. One maintains phosphorylation of the channel and the other becomes apparent when the distal carboxyl‐terminal tail is removed." @default.
- W2582148964 created "2017-02-03" @default.
- W2582148964 creator A5001591717 @default.
- W2582148964 creator A5002922679 @default.
- W2582148964 creator A5086725439 @default.
- W2582148964 date "2017-03-13" @default.
- W2582148964 modified "2023-10-12" @default.
- W2582148964 title "Calmodulin and ATP support activity of the Cav1.2 channel through dynamic interactions with the channel" @default.
- W2582148964 cites W1507991606 @default.
- W2582148964 cites W1604986533 @default.
- W2582148964 cites W1607183863 @default.
- W2582148964 cites W1628979938 @default.
- W2582148964 cites W1971620257 @default.
- W2582148964 cites W1974697878 @default.
- W2582148964 cites W1975980126 @default.
- W2582148964 cites W1979383994 @default.
- W2582148964 cites W1979507652 @default.
- W2582148964 cites W1983861238 @default.
- W2582148964 cites W1987533625 @default.
- W2582148964 cites W1993025208 @default.
- W2582148964 cites W1994172757 @default.
- W2582148964 cites W1995946312 @default.
- W2582148964 cites W1996587443 @default.
- W2582148964 cites W1997413420 @default.
- W2582148964 cites W1998689607 @default.
- W2582148964 cites W2004535935 @default.
- W2582148964 cites W2006701547 @default.
- W2582148964 cites W2008250931 @default.
- W2582148964 cites W2009765916 @default.
- W2582148964 cites W2012301429 @default.
- W2582148964 cites W2015593651 @default.
- W2582148964 cites W2026691793 @default.
- W2582148964 cites W2032234475 @default.
- W2582148964 cites W2045715489 @default.
- W2582148964 cites W2050824263 @default.
- W2582148964 cites W2053330127 @default.
- W2582148964 cites W2055098453 @default.
- W2582148964 cites W2057269307 @default.
- W2582148964 cites W2060517395 @default.
- W2582148964 cites W2065919027 @default.
- W2582148964 cites W2079237232 @default.
- W2582148964 cites W2079827686 @default.
- W2582148964 cites W2086871275 @default.
- W2582148964 cites W2087062865 @default.
- W2582148964 cites W2096701787 @default.
- W2582148964 cites W2097659472 @default.
- W2582148964 cites W2099753276 @default.
- W2582148964 cites W2115955927 @default.
- W2582148964 cites W2117767094 @default.
- W2582148964 cites W2125642130 @default.
- W2582148964 cites W2133173713 @default.
- W2582148964 cites W2135015186 @default.
- W2582148964 cites W2139087276 @default.
- W2582148964 cites W2151769410 @default.
- W2582148964 cites W2159348191 @default.
- W2582148964 cites W2161749263 @default.
- W2582148964 cites W2162072792 @default.
- W2582148964 cites W2163643629 @default.
- W2582148964 cites W2168897337 @default.
- W2582148964 cites W2169653175 @default.
- W2582148964 cites W2223789745 @default.
- W2582148964 cites W2291975356 @default.
- W2582148964 cites W2333729205 @default.
- W2582148964 cites W2426611130 @default.
- W2582148964 doi "https://doi.org/10.1113/jp273736" @default.
- W2582148964 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5390892" @default.
- W2582148964 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28130847" @default.
- W2582148964 hasPublicationYear "2017" @default.
- W2582148964 type Work @default.
- W2582148964 sameAs 2582148964 @default.
- W2582148964 citedByCount "6" @default.
- W2582148964 countsByYear W25821489642018 @default.
- W2582148964 countsByYear W25821489642019 @default.
- W2582148964 countsByYear W25821489642021 @default.
- W2582148964 countsByYear W25821489642023 @default.
- W2582148964 crossrefType "journal-article" @default.
- W2582148964 hasAuthorship W2582148964A5001591717 @default.
- W2582148964 hasAuthorship W2582148964A5002922679 @default.
- W2582148964 hasAuthorship W2582148964A5086725439 @default.
- W2582148964 hasBestOaLocation W25821489641 @default.
- W2582148964 hasConcept C104292427 @default.
- W2582148964 hasConcept C104317684 @default.
- W2582148964 hasConcept C12554922 @default.
- W2582148964 hasConcept C143065580 @default.
- W2582148964 hasConcept C170493617 @default.
- W2582148964 hasConcept C174510640 @default.
- W2582148964 hasConcept C181199279 @default.
- W2582148964 hasConcept C185592680 @default.
- W2582148964 hasConcept C2776972302 @default.
- W2582148964 hasConcept C29688787 @default.
- W2582148964 hasConcept C55493867 @default.
- W2582148964 hasConcept C86803240 @default.
- W2582148964 hasConcept C95444343 @default.
- W2582148964 hasConceptScore W2582148964C104292427 @default.
- W2582148964 hasConceptScore W2582148964C104317684 @default.
- W2582148964 hasConceptScore W2582148964C12554922 @default.
- W2582148964 hasConceptScore W2582148964C143065580 @default.
- W2582148964 hasConceptScore W2582148964C170493617 @default.