title: Rundown of somatodendritic N-methyl-D-aspartate (NMDA) receptor channels in rat hippocampal neurones: evidence for a role of the small GTPase RhoA.
abstract: Actin filament (F-actin) depolymerization leads to the use-dependent rundown of N-methyl-D-aspartate (NMDA) receptor activity in rat hippocampal neurones. Depolymerization is promoted by Ca2+ which enters the cells via NMDA receptor channels. The ras homologue (Rho) GTPases (RhoA, Rac1 and Cdc42) promote actin polymerization and thus control the actin cytoskeleton. We have investigated, by means of the whole-cell patch clamp technique, whether the actin fibres which interact with NMDA receptors are controlled by Rho GTPases. In the presence of intracellular ATP which attenuates rundown, the C3 toxin from Clostridium (C.) botulinum was used to inactivate RhoA. Indeed, it enhanced the use-dependent rundown of NMDA-evoked inward currents to a level similar to that obtained in the absence of ATP. Lethal toxin from Clostridium sordellii which inactivates Rac1 and Cdc42 lacked this effect. We suggest that the function of somatodendritic NMDA receptor channels in rat hippocampal neurones can be modulated by RhoA via its action on F-actin.
authors.affiliation: Department of Pharmacology, Albert-Ludwigs-University, Freiburg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Nörenberg
authors.forename: F
authors.initials: F
authors.lastname: Hofmann
authors.forename: P
authors.initials: P
authors.lastname: Illes
authors.forename: K
authors.initials: K
authors.lastname: Aktories
authors.forename: D K
authors.initials: DK
authors.lastname: Meyer
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D003712:Dendrites / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D020742:rhoA GTP-Binding Protein
chemical_list: D000199:Actins; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein