Meeting Abstract
P2.130 Thursday, Jan. 5 Adenylyl Cyclase Inhibitors Reverse the Neurotoxic Effects of Manganese on Post-Synaptic Dopamine D2 Receptors NELSON, M.*; ADAMS, T.; OJO, C.O.; CARROLL, M.A.; CATAPANE, E.J.; Medgar Evers College, Brooklyn, NY; Medgar Evers College, Brooklyn, NY; Kingsborough Community College, Brooklyn, NY; Medgar Evers College, Brooklyn, NY; Medgar Evers College, Brooklyn, NY margie@mec.cuny.edu
Manganese (Mn), a neurotoxin causing Manganism, a Parkinsons-like disease, disrupts dopaminergic systems. The mechanism is not fully resolved. Gill lateral cilia of Crassostrea virginica are controlled by serotonergic-dopaminergic innervations from their ganglia. Dopamine (DA) is cilio-inhibitory, serotonin cilio-excitatory. Previously we showed post-synaptic DA receptors in gill lateral cells are D2 type, G protein-coupled (Gai/o) metabotropic receptors. Gai inhibits adenylyl cyclase (AC). Gβγ opens K+ and closes Ca2+ channels. We showed Mn blocks DA post-synaptic receptor activity. Here we observed membrane potentials of gill lateral ciliated cells of C. virginica with a fluorescent dye while measuring cilia beating rates. Applying serotonin to gill caused prolonged membrane depolarization and increased cilia beating rates. Applying DA after exciting cilia repolarized the membrane and decreased beating. Mn prevented the cilio-inhibitory response and repolarization. Applying ATP (10-4M) or forskolin (10-6-10-5M), an AC activator, to control or Mn treated gills increased beating without changing membrane potential. Applying MDL or SQ (10-5-10-2M, AC inhibitors, to controls or Mn treated gills decreased beating without affecting membrane potential. The study shows a correlation between membrane potential and cilia beating rates; that actions initiated by activation of D2 post-synaptic receptors can be differentiated to effects on AC and membrane potential; and neurotoxic effects of Mn can be overcome by AC inhibitors. This information is helpful to understand causes and treatments of Manganism.
