FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2891068369> ?p ?o ?g. }

• W2891068369 abstract "Background Oxidative stress–mediated Ca 2+ /calmodulin‐dependent protein kinase II (Ca MKII) phosphorylation of cardiac ion channels has emerged as a critical contributor to arrhythmogenesis in cardiac pathology. However, the link between mitochondrial‐derived reactive oxygen species (md ROS ) and increased Ca MKII activity in the context of cardiac arrhythmias has not been fully elucidated and is difficult to establish experimentally. Methods and Results We hypothesize that pathological md ROS can cause erratic action potentials through the oxidation‐dependent Ca MKII activation pathway. We further propose that Ca MKII ‐dependent phosphorylation of sarcolemmal slow Na + channels alone is sufficient to elicit early afterdepolarizations. To test the hypotheses, we expanded our well‐established guinea pig cardiomyocyte e xcitation‐ c ontraction coupling, m itochondrial e nergetics, and R OS ‐ i nduced‐ R OS ‐ r elease model by incorporating oxidative Ca MKII activation and Ca MKII ‐dependent Na + channel phosphorylation in silico. Simulations show that md ROS mediated‐Ca MKII activation elicits early afterdepolarizations by augmenting the late Na + currents, which can be suppressed by blocking L‐type Ca 2+ channels or Na + /Ca 2+ exchangers. Interestingly, we found that oxidative Ca MKII activation–induced early afterdepolarizations are sustained even after md ROS has returned to its physiological levels. Moreover, mitochondrial‐targeting antioxidant treatment can suppress the early afterdepolarizations, but only if given in an appropriate time window. Incorporating concurrent md ROS ‐induced ryanodine receptors activation further exacerbates the proarrhythmogenic effect of oxidative Ca MKII activation. Conclusions We conclude that oxidative Ca MKII activation–dependent Na channel phosphorylation is a critical pathway in mitochondria‐mediated cardiac arrhythmogenesis." @default.
• W2891068369 created "2018-09-27" @default.
• W2891068369 creator A5013361951 @default.
• W2891068369 creator A5015146106 @default.
• W2891068369 creator A5022234641 @default.
• W2891068369 creator A5022429262 @default.
• W2891068369 creator A5038710409 @default.
• W2891068369 creator A5059853274 @default.
• W2891068369 creator A5082669345 @default.
• W2891068369 creator A5091603253 @default.
• W2891068369 date "2018-08-07" @default.
• W2891068369 modified "2023-10-14" @default.
• W2891068369 title "Mitochondrial‐Mediated Oxidative Ca ²⁺ /Calmodulin‐Dependent Kinase II Activation Induces Early Afterdepolarizations in Guinea Pig Cardiomyocytes: An In Silico Study" @default.
• W2891068369 cites W1517242685 @default.
• W2891068369 cites W1518655170 @default.
• W2891068369 cites W1601307541 @default.
• W2891068369 cites W1690146698 @default.
• W2891068369 cites W1964430604 @default.
• W2891068369 cites W1964847650 @default.
• W2891068369 cites W1966481559 @default.
• W2891068369 cites W1967380913 @default.
• W2891068369 cites W1970380177 @default.
• W2891068369 cites W1980306855 @default.
• W2891068369 cites W1983906605 @default.
• W2891068369 cites W1990575884 @default.
• W2891068369 cites W1990723202 @default.
• W2891068369 cites W1991992462 @default.
• W2891068369 cites W1992290425 @default.
• W2891068369 cites W2006094057 @default.
• W2891068369 cites W2010507283 @default.
• W2891068369 cites W2020063160 @default.
• W2891068369 cites W2021235911 @default.
• W2891068369 cites W2023144609 @default.
• W2891068369 cites W2024287748 @default.
• W2891068369 cites W2033594768 @default.
• W2891068369 cites W2035968737 @default.
• W2891068369 cites W2037862835 @default.
• W2891068369 cites W2039440815 @default.
• W2891068369 cites W2040337560 @default.
• W2891068369 cites W2040846930 @default.
• W2891068369 cites W2043264021 @default.
• W2891068369 cites W2058028795 @default.
• W2891068369 cites W2077707410 @default.
• W2891068369 cites W2080150505 @default.
• W2891068369 cites W2080314993 @default.
• W2891068369 cites W2082879125 @default.
• W2891068369 cites W2088926748 @default.
• W2891068369 cites W2091583229 @default.
• W2891068369 cites W2092906738 @default.
• W2891068369 cites W2093270911 @default.
• W2891068369 cites W2096545094 @default.
• W2891068369 cites W2098398336 @default.
• W2891068369 cites W2100611216 @default.
• W2891068369 cites W2105649138 @default.
• W2891068369 cites W2105658413 @default.
• W2891068369 cites W2108383919 @default.
• W2891068369 cites W2115765852 @default.
• W2891068369 cites W2116297568 @default.
• W2891068369 cites W2120804597 @default.
• W2891068369 cites W2128908058 @default.
• W2891068369 cites W2129351481 @default.
• W2891068369 cites W2132826785 @default.
• W2891068369 cites W2134506141 @default.
• W2891068369 cites W2138868817 @default.
• W2891068369 cites W2140384407 @default.
• W2891068369 cites W2142256658 @default.
• W2891068369 cites W2153869960 @default.
• W2891068369 cites W2157973908 @default.
• W2891068369 cites W2160448824 @default.
• W2891068369 cites W2161894401 @default.
• W2891068369 cites W2162228881 @default.
• W2891068369 cites W2165537841 @default.
• W2891068369 cites W2165620104 @default.
• W2891068369 cites W2168556429 @default.
• W2891068369 cites W2171595000 @default.
• W2891068369 cites W2177044742 @default.
• W2891068369 cites W2337457656 @default.
• W2891068369 cites W2343255364 @default.
• W2891068369 cites W2399644778 @default.
• W2891068369 cites W2559792655 @default.
• W2891068369 cites W2745546719 @default.
• W2891068369 cites W2891068369 @default.
• W2891068369 doi "https://doi.org/10.1161/jaha.118.008939" @default.
• W2891068369 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6201444" @default.
• W2891068369 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30371234" @default.
• W2891068369 hasPublicationYear "2018" @default.
• W2891068369 type Work @default.
• W2891068369 sameAs 2891068369 @default.
• W2891068369 citedByCount "11" @default.
• W2891068369 countsByYear W28910683692018 @default.
• W2891068369 countsByYear W28910683692019 @default.
• W2891068369 countsByYear W28910683692020 @default.
• W2891068369 countsByYear W28910683692021 @default.
• W2891068369 countsByYear W28910683692022 @default.
• W2891068369 countsByYear W28910683692023 @default.
• W2891068369 crossrefType "journal-article" @default.
• W2891068369 hasAuthorship W2891068369A5013361951 @default.
• W2891068369 hasAuthorship W2891068369A5015146106 @default.
• W2891068369 hasAuthorship W2891068369A5022234641 @default.
• W2891068369 hasAuthorship W2891068369A5022429262 @default.

• next