![]() |
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received for publication February 22, 2006.
Revised March 21, 2006.
Accepted for publication March 23, 2006.
Choline is an essential nutrient and a precursor of neurotransmitter ACh and is produced at synapses during depolarization, upon hydrolysis of ACh via acetylcholinesterase, and under conditions of injury and trauma. Animal studies have shown that supplementation with choline during early development results in long-lasting improvement in memory in adults; however, the mechanisms underlying this effect are poorly defined. Previous studies revealed that choline interacts with type IA (
7*) nicotinic acetylcholine receptors (nAChRs) as a full agonist and as a desensitizing agent, and is a weak agonist of type III (
3
4*) nAChRs. Since nAChRs play a role in learning and memory and are generally inhibited by agonists at low concentrations, we investigated in this study the inhibitory effects of choline on non-
7 nAChRs such as type II (
4
2*) and type III nAChRs. Using whole-cell patch-clamp recordings from neurons of rat hippocampal and dorsal striatal slices, we demonstrate that choline inhibits type III nAChR-mediated glutamate EPSCs. Choline inhibited ACh-induced NMDA EPSCs in CA1 stratum radiatum (SR) interneurons of rat hippocampal slices with an IC50 of
15 µM. Choline did not inhibit NMDA or AMPA receptors in CA1 SR interneurons. Choline inhibited type II nAChRs in CA1 SR interneurons with an IC50 of
370 µM. The present results reveal an order of inhibitory potency for choline type III >type IA > type II nAChRs. It is concluded that brain nAChRs, but not glutamate receptors, are the primary targets for the regulatory actions of choline.
Key words:
AMPA EPSC, Betaine, NMDA EPSC, choline, nicotinic receptors, rat hippocampal slices
This article has been cited by other articles:
![]() |
N. Innocent, P. D. Livingstone, A. Hone, A. Kimura, T. Young, P. Whiteaker, J. M. McIntosh, and S. Wonnacott {alpha}Conotoxin Arenatus IB[V11l,V16D] Is a Potent and Selective Antagonist at Rat and Human Native {alpha}7 Nicotinic Acetylcholine Receptors J. Pharmacol. Exp. Ther., November 1, 2008; 327(2): 529 - 537. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Alkondon, E. F. R. Pereira, M. C. Potter, F. C. Kauffman, R. Schwarcz, and E. X. Albuquerque Strain-Specific Nicotinic Modulation of Glutamatergic Transmission in the CA1 Field of the Rat Hippocampus: August Copenhagen Irish Versus Sprague-Dawley J Neurophysiol, February 1, 2007; 97(2): 1163 - 1170. [Abstract] [Full Text] [PDF] |
||||