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• W2002474522 abstract "Cav1.2 and Cav1.3 are the main L-type Ca(2+) channel subtypes in the brain. Cav1.3 channels have recently been implicated in the pathogenesis of Parkinson's disease. Therefore, Cav1.3-selective blockers are developed as promising neuroprotective drugs. We studied the pharmacological properties of a pyrimidine-2,4,6-trione derivative (1-(3-chlorophenethyl)-3-cyclopentylpyrimidine-2,4,6-(1H,3H,5H)-trione, Cp8) recently reported as the first highly selective Cav1.3 blocker. Here we show, in contrast to this previous study, that Cp8 reproducibly increases inward Ca(2+) currents of Cav1.3 and Cav1.2 channels expressed in tsA-201 cells by slowing activation, inactivation and enhancement of tail currents. Similar effects are also observed for native Cav1.3 and Cav1.2 channels in mouse chromaffin cells, while non-L-type currents are unaffected. Evidence for a weak and non-selective inhibition of Cav1.3 and Cav1.2 currents is only observed in a minority of cells using Ba(2+) as charge carrier. Therefore, our data identify pyrimidine-2,4,6-triones as Ca(2+) channel activators." @default.
• W2002474522 created "2016-06-24" @default.
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• W2002474522 date "2014-06-19" @default.
• W2002474522 modified "2023-09-26" @default.
• W2002474522 title "Pyrimidine-2,4,6-triones are a new class of voltage-gated L-type Ca2+ channel activators" @default.
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• W2002474522 doi "https://doi.org/10.1038/ncomms4897" @default.
• W2002474522 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4083433" @default.
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