Physiological and pharmacological characterization of a molluscan neuronal efflux transporter; evidence for age-related transporter impairment

Abstract

Plasma membrane efflux transporters play crucial roles in the removal and release of harmful but also beneficial substances from the interior of cells and tissue types in virtually every extant species. They contribute to the clearance of a broad spectrum of exogenous and endogenous toxicants and harmful metabolites including the reactive lipid aldehyde byproducts of lipid peroxidation that are a hallmark of cellular aging. Here we tested whether declining transporter functionality may contribute to functional decline in a snail model of neuronal aging. Through measuring the removal of 5(6)-carboxyfluorescein, a known substrate for membrane efflux transporters, we provide, for the first time, physiological evidence for the existence of probenecid-, MK571- and glutathione-sensitive efflux transporters in (gastropod) neurons and demonstrate that their functionality declines with age. Our data supports the idea that waning cellular detoxification capacity might be a significant factor in the escalation of (lipo-)toxicity observed in neuronal aging.