Acetylcholine precursor choline evokes NMDA-dependent epileptoid activity in rat hippocampal CA1 area.
Application of choline (5 and 10 mM) to electrically stimulated (1 Hz) rat hippocampal slices evoked epileptoid activity manifested by generation of extra population spikes. Application of methyllycaconitine (10 nM), a specific agonist for α7-subunit of nicotinic acetylcholine receptors, did not prevent generation of extra population spikes. In contrast, pretreatment of slices with Mg(2+) (5 mM) or blockade of NMDA-type glutamate receptors with MK-801 (100 μM) prevented generation of the extra population spikes. It was hypothesized that elevation of choline concentration during cerebral pathology can promote activation of NMDA-receptors and provoke epileptoid activity not related to activation of α7-subunit of nicotinic acetylcholine receptor.
State Research Institute of General Pathology and Pathological Physiology, Russian Academy of Medical Sciences, Moscow, Russia. vmotin@hotmail.com
V G
VG
Motin
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000503:physiopathology; D002794:Choline / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D018733:Nicotinic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; C054634:methyllycaconitine; D016291:Dizocilpine Maleate; D002794:Choline; D000157:Aconitine