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This Article Full Text Full Text (PDF) All Versions of this Article: 582/1/359    most recent jphysiol.2007.130617v1 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 Citing Articles via Google Scholar Google Scholar Articles by Morgado-Valle, C. Articles by Feldman, J. L. Search for Related Content PubMed PubMed Citation Articles by Morgado-Valle, C. Articles by Feldman, J. L. Related Collections Respiratory

¹ Systems Neurobiology Laboratory, Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Box 951763, Los Angeles, CA 90095-1763, USA

The role of AMPA receptors (AMPARs) in generation and propagation of respiratory rhythm is well documented both in vivo and in vitro, whereas the functional significance of NMDA receptors (NMDARs) in preBötzinger complex (preBötC) neurons has not been explored. Here we examined the interactions between AMPARs and NMDARs during spontaneous respiratory rhythm generation in slices from neonatal rats in vitro. We tested the hypothesis that activation of NMDARs can drive respiratory rhythm in the absence of other excitatory drives. Blockade of NMDARs with dizocilpine hydrogen maleate (MK-801, 20 µM) had a negligible effect on respiratory rhythm and pattern under standard conditions in vitro, whereas blockade of AMPARs with NBQX (0.5 µM) completely abolished respiratory activity. Removal of extracellular Mg²⁺ to relieve the voltage-dependent block of NMDARs maintained respiratory rhythm without a significant effect on period, even in the presence of high NBQX concentrations ( 100 µM). Removal of Mg²⁺ increased inspiratory-modulated inward current peak (I_I) and charge (Q_I) in preBötC neurons voltage-clamped at –60 mV by 245% and 309%, respectively, with respect to basal values. We conclude that the normal AMPAR-mediated postsynaptic current underlying respiratory drive can be replaced by NMDAR-mediated postsynaptic current when the voltage-dependent Mg²⁺ block is removed. Under this condition, respiratory-related frequency is unaffected by changes in I_I, suggesting that the two can be independently regulated.

(Received 16 February 2007; accepted after revision 16 April 2007; first published online 19 April 2007)
Corresponding author C. Morgado-Valle: Department of Neurobiology, David Geffen School of Medicine at UCLA, Box 951763, Los Angeles, CA 90095-1763, USA. Email: cmorgado{at}mednet.ucla.edu

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