HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 586/23/5727    most recent jphysiol.2008.160622v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Clarke, R. J. Articles by Johnson, J. W. PubMed PubMed Citation Articles by Clarke, R. J. Articles by Johnson, J. W. Related Collections Neuroscience Related Article

¹ Department of Neuroscience and Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA

Ligand-gated ion channels are activated by agonist binding, but may also be modulated by membrane voltage. N-Methyl-D-aspartate receptors (NMDARs) exhibit especially strong voltage dependence due to channel block by external Mg²⁺ (Mg_o²⁺). Here we demonstrate that activity of NMDARs composed of NR1 and NR2B subunits (NR1/2B receptors) is enhanced by depolarization even in 0 Mg_o²⁺, causing slow current relaxations in response to rapid voltage changes. We present a kinetic model of receptor activation that incorporates voltage-dependent gating-associated NR2B subunit conformational changes. The model accurately reproduces current relaxations during depolarizations and subsequent repolarizations in 0 Mg_o²⁺. Model simulations in physiological Mg_o²⁺ concentrations show that voltage-dependent receptor gating also underlies the slow component of Mg_o²⁺ unblock, a phenomenon that previously was shown to influence Mg_o²⁺ unblock kinetics during dendritic spikes. We propose that voltage-dependent gating of NR1/2B receptors confers enhanced voltage and time dependence on NMDAR-mediated signalling.

(Received 28 July 2008; accepted after revision 14 October 2008; first published online 20 October 2008)
Corresponding author J. W. Johnson: Department of Neuroscience and Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA. Email: jjohnson{at}pitt.edu

Related Article

A tingle of extra excitement with voltage dependence of NMDA receptor activation

Alasdair J. Gibb
J. Physiol. 2008 586: 5607. [Full Text] [PDF]

This article has been cited by other articles:

				A. J. Gibb A tingle of extra excitement with voltage dependence of NMDA receptor activation J. Physiol., December 1, 2008; 586(23): 5607 - 5607. [Full Text] [PDF]