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Original Research ARTICLE

Front. Neural Circuits, 29 November 2010 | http://dx.doi.org/10.3389/fncir.2010.00124

Outward currents contributing to inspiratory burst termination in preBötzinger Complex neurons of neonatal mice studied in vitro

  • Department of Applied Science, The College of William and Mary, Williamsburg, VA, USA

We studied preBötzinger Complex (preBötC) inspiratory interneurons to determine the cellular mechanisms that influence burst termination in a mammalian central pattern generator. Neonatal mouse slice preparations that retain preBötC neurons generate respiratory motor rhythms in vitro. Inspiratory-related bursts rely on inward currents that flux Na+, thus outward currents coupled to Na+ accumulation are logical candidates for assisting in, or causing, burst termination. We examined Na+/K+ ATPase electrogenic pump current (Ipump), Na+-dependent K+ current (IK–Na), and ATP-dependent K+ current (IK–ATP). The pharmacological blockade of Ipump, IK–Na, or IK–ATP caused pathological depolarization akin to a burst that cannot terminate, which impeded respiratory rhythm generation and reversibly stopped motor output. By simulating inspiratory bursts with current-step commands in synaptically isolated preBötC neurons, we determined that each current generates approximately 3–8 mV of transient post-burst hyperpolarization that decays in 50–1600 ms. Ipump, IK–Na, and – to a lesser extent – IK–ATP contribute to terminating inspiratory bursts in the context of respiratory rhythm generation by responding to activity dependent cues such as Na+ accumulation.

Keywords: central pattern generation, breathing, respiration, brainstem, rhythmic networks, Na/K ATPase, sodium-dependent potassium current, ATP-dependent potassium current

Citation: Krey RA, Goodreau AM, Arnold TB and Del Negro CA (2010) Outward currents contributing to inspiratory burst termination in preBötzinger Complex neurons of neonatal mice studied in vitro. Front. Neural Circuits 4:124. doi: 10.3389/fncir.2010.00124

Received: 29 September 2010; Paper pending published: 20 October 2010;
Accepted: 11 November 2010; Published online: 29 November 2010.

Edited by:

Paul S. Katz, Georgia State University, USA

Reviewed by:

Stephen M. Johnson, University of Wisconsin, USA
Gregory D. Funk, University of Alberta, Canada

Copyright: © 2010 Krey, Goodreau, Arnold and Del Negro. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

*Correspondence: Christopher A. Del Negro, Department of Applied Science, The College of William and Mary, McGlothlin-Street Hall, Room 318, Williamsburg, VA 23187-8795, USA. e-mail: cadeln@wm.edu