Effects of Pb2+ on muscarinic modulation of glutamatergic synaptic transmission in rat hippocampal CA1 area.
Lead (Pb(2+)) is a pollutant commonly found in the environment. It causes a wide variety of detrimental effects on developing central nervous system. However, the mechanisms of its neurotoxicity remained to be elucidated. In hippocampus, the muscarinic cholinergic system modulates certain forms of synaptic transmission and plasticity, and plays an important role in learning and memory. In this study, the effects of Pb(2+) on muscarinic modulation of glutamatergic synaptic transmission in hippocampal CA1 area were investigated using the conventional whole-cell patch-clamp technique in rat hippocampal slices. In the presence of nicotinic antagonist mecamylamine, carbachol (CCh), a cholinergic agonist, concentration-dependently inhibited glutamatergic excitatory postsynaptic currents (EPSCs), enhanced paired-pulse facilitation (PPF) and the response to 10-Hz pulse-trains. The analysis of the spontaneous excitatory postsynaptic currents (sEPSCs) showed the activation of muscarinic receptors by CCh decreased the frequency, amplitude and decay time of sEPSCs. The 10 microM Pb(2+) depressed the inhibition of EPSCs by CCh, reduced the CCh-induced enhancement of PPF and the response to 10-Hz pulse-trains, and also affected the modulation of sEPSCs by CCh. The results suggested that the activation of muscarinic acetylcholine (ACh) receptors in hippocampus could modulate glutamatergic synaptic transmission, while Pb(2+) exposure would lead to an alteration of muscarinic modulation, which might be involved in the Pb(2+)-induced impairment of synaptic transmission and plasticity during learning and memory.
Wang
Lang
L
Department of Neurobiology & Biophysics, School of Life Science, University of Science & Technology of China, Hefei, Anhui 230027, PR China.
Luo
Le
L
Luo
Yun-Yun
YY
Gu
Yan
Y
Ruan
Di-Yun
DY
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D005971:Glutamates / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D020263:Lead Poisoning, Nervous System / Q000503:physiopathology*; D007858:Learning / Q000187:drug effects; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D008568:Memory / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D002217:Carbachol; D018756:GABA Antagonists; D005971:Glutamates; D008464:Mecamylamine; D018721:Muscarinic Agonists; D018733:Nicotinic Antagonists; D010852:Picrotoxin; D011976:Receptors, Muscarinic