Lead Mediates Concentration-Dependent Inhibition at mGluR7a Receptors but Does Not Cause Significant Changes at GlyR Alpha 1 in Xenopus Oocytes

Abstract

Exposure to the environmental toxin Pb has detrimental effects on humans even at low blood Pb levels. Pb exposure remains a public health concern in developed nations and is becoming a greater problem in developing nations. High blood Pb levels can lead to cognitive deficits, especially in children. Previous work has described the effects of lead on brain neurotransmitter systems. We hypothesized that Pb would modulate two neurotransmitter receptors: the metabotropic glutamate receptor mGluR7a and the ionotropic glycine receptor GlyR alpha 1. Using two-electrode voltage clamp in Xenopus oocytes, previous team members found concentration-dependent inhibition at mGluR7a. In addition, there was a rightward shift in the concentration-response curves for glutamate in the presence of Pb suggesting that the Pb interacts in either a competitive or mixed manner at the mGluR7a. For glycine receptors, previous studies show effects of divalent ions such as Cu2+ and Fe2+, however, our study found no statistically significant differences between the presence and absence of Pb on the function of GlyR alpha 1 receptor. These studies show that Pb’s actions on neurotransmitter receptors is specific. Our results may in part explain how Pb causes cognitive problems by modulating neurotransmitter receptors in the brain.