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Inspiratory bursts in the preBötzinger complex depend on a calcium-activated non-specific cation current linked to glutamate receptors in neonatal mice
Article first published online: 25 JUN 2007
The Journal of Physiology
Volume 582, Issue 1, pages 113–125, July 2007
How to Cite
Pace, R. W., Mackay, D. D., Feldman, J. L. and Del Negro, C. A. (2007), Inspiratory bursts in the preBötzinger complex depend on a calcium-activated non-specific cation current linked to glutamate receptors in neonatal mice. The Journal of Physiology, 582: 113–125. doi: 10.1113/jphysiol.2007.133660
- Issue published online: 25 JUN 2007
- Article first published online: 25 JUN 2007
- (Resubmitted 29 March 2007; accepted 17 April 2007; first published online 19 April 2007)
Inspiratory neurons of the preBötzinger complex (preBötC) form local excitatory networks and display 10–30 mV transient depolarizations, dubbed inspiratory drive potentials, with superimposed spiking. AMPA receptors are critical for rhythmogenesis under normal conditions in vitro but whether other postsynaptic mechanisms contribute to drive potential generation remains unknown. We examined synaptic and intrinsic membrane properties that generate inspiratory drive potentials in preBötC neurons using neonatal mouse medullary slice preparations that generate respiratory rhythm. We found that NMDA receptors, group I metabotropic glutamate receptors (mGluRs), but not group II mGluRs, contributed to inspiratory drive potentials. Subtype 1 of the group I mGluR family (mGluR1) probably regulates a K+ channel, whereas mGluR5 operates via an inositol 1,4,5-trisphosphate (IP3) receptor-dependent mechanism to augment drive potential generation. We tested for and verified the presence of a Ca2+-activated non-specific cation current (ICAN) in preBötC neurons. We also found that high concentrations of intracellular BAPTA, a high-affinity Ca2+ chelator, and the ICAN antagonist flufenamic acid (FFA) decreased the magnitude of drive potentials. We conclude that ICAN underlies robust inspiratory drive potentials in preBötC neurons, and is only fully evoked by ionotropic and metabotropic glutamatergic synaptic inputs, i.e. by network activity.