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J Physiol Volume 586, Number 9, 2357-2370, May 1, 2008 DOI: 10.1113/jphysiol.2007.150532
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RESPIRATORY

Distinct receptors underlie glutamatergic signalling in inspiratory rhythm-generating networks and motor output pathways in neonatal rat

 M. F. Ireland1, F. C. Lenal1,2, A. R. Lorier1,3, D. E. Loomes1, T. Adachi1, T. S. Alvares1, J. J. Greer1,2 and G. D. Funk1,2,3

1 Department of Physiology
2 Centre for Neuroscience, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
3 Division of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, Private Bag 92019, New Zealand

Despite the enormous diversity of glutamate (Glu) receptors and advances in understanding recombinant receptors, native Glu receptors underlying functionally identified inputs in active systems are poorly defined in comparison. In the present study we use UBP-302, which antagonizes GluR5 subunit-containing kainate (KA) receptors at ≤ 10 µM, but other KA and AMPA receptors at ≥ 100 µM, and rhythmically active in vitro preparations of neonatal rat to explore the contribution of non-NMDA receptor signalling in rhythm-generating and motor output compartments of the inspiratory network. At 10 µM, UBP-302 had no effect on inspiratory burst frequency or amplitude. At 100 µM, burst amplitude recorded from XII, C1 and C4 nerve roots was significantly reduced, but frequency was unaffected. The lack of a frequency effect was confirmed when local application of UBP-302 (100 µM) into the pre-Bötzinger complex (preBötC) did not affect frequency but substance P evoked a 2-fold increase. A UBP-302-sensitive (10 µM), ATPA-evoked frequency increase, however, established that preBötC networks are sensitive to GluR5 activation. Whole-cell recordings demonstrated that XII motoneurons also express functional GluR5-containing KA receptors that do not contribute to inspiratory drive, and confirmed the dose dependence of UBP-302 actions on KA and AMPA receptors. Our data provide the first evidence that the non-NMDA (most probably AMPA) receptors mediating glutamatergic transmission within preBötC inspiratory rhythm-generating networks are pharmacologically distinct from those transmitting drive to inspiratory motoneurons. This differential expression may ultimately be exploited pharmacologically to separately counteract depression of central respiratory rhythmogenesis or manipulate the drive to motoneurons controlling airway and pump musculature.

(Received 25 December 2007; accepted after revision 12 March 2008; first published online 13 March 2008)
Corresponding author G. D. Funk: 7–50 Medical Sciences Bldg, Department of Physiology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7. Email: gf{at}ualberta.ca

F. C. Lenal and A. R. Lorier contributed equally to this work.






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