Matches in SemOpenAlex for { <https://semopenalex.org/work/W4307942657> ?p ?o ?g. }
- W4307942657 endingPage "13080" @default.
- W4307942657 startingPage "13080" @default.
- W4307942657 abstract "Unidentified pathogenetic mechanisms and genetic and clinical heterogeneity represent critical factors hindering the development of treatments for inherited retinal dystrophies. Frameshift mutations in Cacna2d4, which codes for an accessory subunit of voltage-gated calcium channels (VGCC), cause cone-rod dystrophy RCD4 in patients, but the underlying mechanisms remain unknown. To define its pathogenetic mechanisms, we investigated the impact of a Cacna2d4 frameshift mutation on the electrophysiological profile and calcium handling of mouse rod photoreceptors by patch-clamp recordings and calcium imaging, respectively. In mutant (MUT) rods, the dysregulation of calcium handling extends beyond the reduction in calcium entry through VGCC and surprisingly involves internal calcium stores' depletion and upregulation of calcium entry via non-selective cationic channels (CSC). The similar dependence of CSC on basal calcium levels in WT and MUT rods suggests that the primary defect in MUT rods lies in defective calcium stores. Calcium stores' depletion, leading to upregulated calcium and sodium influx via CSC, represents a novel and, so far, unsuspected consequence of the Cacna2d4 mutation. Blocking CSC may provide a novel strategy to counteract the well-known pathogenetic mechanisms involved in rod demise, such as the reticulum stress response and calcium and sodium overload due to store depletion." @default.
- W4307942657 created "2022-11-06" @default.
- W4307942657 creator A5032350625 @default.
- W4307942657 creator A5045448349 @default.
- W4307942657 creator A5048966022 @default.
- W4307942657 date "2022-10-28" @default.
- W4307942657 modified "2023-10-01" @default.
- W4307942657 title "Depleted Calcium Stores and Increased Calcium Entry in Rod Photoreceptors of the Cacna2d4 Mouse Model of Cone-Rod Dystrophy RCD4" @default.
- W4307942657 cites W114264706 @default.
- W4307942657 cites W1489656485 @default.
- W4307942657 cites W1490352649 @default.
- W4307942657 cites W1493682555 @default.
- W4307942657 cites W1498303838 @default.
- W4307942657 cites W1529590189 @default.
- W4307942657 cites W1544777143 @default.
- W4307942657 cites W1556624435 @default.
- W4307942657 cites W1575417106 @default.
- W4307942657 cites W1584547533 @default.
- W4307942657 cites W1587923301 @default.
- W4307942657 cites W1593385535 @default.
- W4307942657 cites W1602155299 @default.
- W4307942657 cites W1603282309 @default.
- W4307942657 cites W1795554797 @default.
- W4307942657 cites W1921440755 @default.
- W4307942657 cites W1949292176 @default.
- W4307942657 cites W1964645175 @default.
- W4307942657 cites W1965185652 @default.
- W4307942657 cites W1965589632 @default.
- W4307942657 cites W1977584840 @default.
- W4307942657 cites W1977823409 @default.
- W4307942657 cites W1978070679 @default.
- W4307942657 cites W1985069323 @default.
- W4307942657 cites W1987458637 @default.
- W4307942657 cites W1988297454 @default.
- W4307942657 cites W1990335273 @default.
- W4307942657 cites W2000459815 @default.
- W4307942657 cites W2003295643 @default.
- W4307942657 cites W2003897295 @default.
- W4307942657 cites W2005049319 @default.
- W4307942657 cites W2013077952 @default.
- W4307942657 cites W2019157571 @default.
- W4307942657 cites W2021341720 @default.
- W4307942657 cites W2023362787 @default.
- W4307942657 cites W2024002523 @default.
- W4307942657 cites W2026544879 @default.
- W4307942657 cites W2026665944 @default.
- W4307942657 cites W2028803712 @default.
- W4307942657 cites W2029657491 @default.
- W4307942657 cites W2030068415 @default.
- W4307942657 cites W2041384212 @default.
- W4307942657 cites W2042469463 @default.
- W4307942657 cites W2044199904 @default.
- W4307942657 cites W2045519476 @default.
- W4307942657 cites W2055418337 @default.
- W4307942657 cites W2063802036 @default.
- W4307942657 cites W2064341918 @default.
- W4307942657 cites W2064528191 @default.
- W4307942657 cites W2066827598 @default.
- W4307942657 cites W2073097593 @default.
- W4307942657 cites W2077095149 @default.
- W4307942657 cites W2082358146 @default.
- W4307942657 cites W2093661120 @default.
- W4307942657 cites W2099834228 @default.
- W4307942657 cites W2100688705 @default.
- W4307942657 cites W2103224021 @default.
- W4307942657 cites W2109800651 @default.
- W4307942657 cites W2124795976 @default.
- W4307942657 cites W2126379315 @default.
- W4307942657 cites W2128270335 @default.
- W4307942657 cites W2129714795 @default.
- W4307942657 cites W2130496406 @default.
- W4307942657 cites W2131117641 @default.
- W4307942657 cites W2135300477 @default.
- W4307942657 cites W2141989757 @default.
- W4307942657 cites W2150091977 @default.
- W4307942657 cites W2152681129 @default.
- W4307942657 cites W2153899225 @default.
- W4307942657 cites W2191080976 @default.
- W4307942657 cites W2218936705 @default.
- W4307942657 cites W2261169281 @default.
- W4307942657 cites W2286323087 @default.
- W4307942657 cites W2395427107 @default.
- W4307942657 cites W2412094990 @default.
- W4307942657 cites W2594557659 @default.
- W4307942657 cites W2613793199 @default.
- W4307942657 cites W2805166789 @default.
- W4307942657 cites W2892303845 @default.
- W4307942657 cites W2901386532 @default.
- W4307942657 cites W2966440218 @default.
- W4307942657 cites W3005260758 @default.
- W4307942657 cites W3085926716 @default.
- W4307942657 cites W3092039862 @default.
- W4307942657 cites W3153986207 @default.
- W4307942657 cites W3200993092 @default.
- W4307942657 cites W4220907516 @default.
- W4307942657 cites W4220995186 @default.
- W4307942657 cites W4232596251 @default.
- W4307942657 cites W4322703181 @default.