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Received March 29, 2007
Revised April 17, 2007
Accepted after revision April 17, 2007
1 College of William and Mary
2 University of California
3 The College of William and Mary
* To whom correspondence should be addressed. E-mail: cadeln{at}wm.edu.
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) likely regulates a K+ channel, whereas mGluR5 operates via an inositol 1,4,5-triphosphate (IP3) receptor-dependent mechanism to augment drive potential generation. We tested for and verified the presence of a Ca2+-activated non-specific cationic 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.
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