Enantioselectivity of 2,2',3,5',6-Pentachlorobiphenyl (PCB 95) Atropisomers toward Ryanodine Receptors (RyRs) and Their Influences on Hippocampal Neuronal Networks.

ABSTRACT: Nineteen ortho-substituted PCBs are chiral and found enantioselectively enriched in ecosystems. Their differential actions on biological targets are not understood. PCB 95 (2,2',3,5',6-pentachlorobiphenyl), a chiral PCB of current environmental relevance, is among the most potent toward modifying ryanodine receptors (RyR) function and Ca²⁺ signaling. PCB 95 enantiomers are separated and assigned aR- and aS-PCB 95 using three chiral-column HPLC and circular dichroism spectroscopy. Studies of RyR1-enriched microsomes show aR-PCB 95 with >4× greater potency (EC₅₀ = 0.20 ± 0.05 μM), ∼ 1.3× higher efficacy (B_max = 3.74 ± 0.07 μM) in [³H]Ryanodine-binding and >3× greater rates (R = 7.72 ± 0.31 nmol/sec/mg) of Ca²⁺ efflux compared with aS-PCB

SUBMITTER: Feng W 

PROVIDER: S-EPMC6251309 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature