Substance P-mediated modulation of pacemaker properties in the mammalian respiratory network

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Fernando Peña, Jan-Marino Ramirez

Abstract

Neuromodulators are integral parts of a neuronal network, and unraveling how these substances alter neuronal activity is critical for understanding how networks generate patterned activity and, ultimately, behavior. In this study, we examined the cellular mechanisms underlying the excitatory action of substance P (SP) on the respiratory network isolated in spontaneously active transverse slice preparation of mice. SP produced a slow depolarization in all recorded inspiratory pacemaker and non-pacemaker neurons. Ion exchange experiments and blockers for different ion channels suggest that the slow depolarization is caused by the activation of a low-threshold TTX-insensitive cationic current that carries mostly Na+. The SP-induced slow depolarization increased tonic discharge in non-pacemaker neurons and primarily enhanced the frequency of bursting in Cd2+-insensitive pacemaker neurons. In the Cd2+-sensitive pacemaker neuron, the burst frequency was not significantly affected, whereas burst duration and amplitude were more enhanced than in Cd2+-insensitive pacemaker neurons. In a subset of non-pacemaker neurons that produced NMDA-dependent subthreshold oscillations, SP caused the production of bursts of action potentials. We conc...Continue Reading

Citations

Oct 24, 2009·Behavior Genetics·Jean-Christophe Roux, Laurent Villard
Jun 2, 2012·Journal of Biological Physics·Jan-Marino RamirezSebastien Zanella
Feb 24, 2006·Nature Reviews. Neuroscience·Jack L Feldman, Christopher A Del Negro
Aug 5, 2009·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Claudio CoddouJaime Eugenín
Oct 2, 2009·Clinical and Experimental Pharmacology & Physiology·Fernando Peña
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