Pyrimidine-2,4,6-triones are a new class of voltage-gated L-type Ca 2+ channel activators

49Citations
Citations of this article
61Readers
Mendeley users who have this article in their library.

Abstract

Cav1.2 and Cav1.3 are the main L-type Ca2+ channel subtypes in the brain. Cav1.3 channels have recently been implicated in the pathogenesis of Parkinsonâ €™ 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 Ca2+ 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 Ba2+ as charge carrier. Therefore, our data identify pyrimidine-2,4,6-triones as Ca2+ channel activators. © 2014 Macmillan Publishers Limited. All rights reserved.

Cite

CITATION STYLE

APA

Ortner, N. J., Bock, G., Vandael, D. H. F., Mauersberger, R., Draheim, H. J., Gust, R., … Striessnig, J. (2014). Pyrimidine-2,4,6-triones are a new class of voltage-gated L-type Ca 2+ channel activators. Nature Communications, 5. https://doi.org/10.1038/ncomms4897

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free