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Front Neural Circuits. 2010 Nov 29;4:124. doi: 10.3389/fncir.2010.00124. eCollection 2010.

Outward Currents Contributing to Inspiratory Burst Termination in preBötzinger Complex Neurons of Neonatal Mice Studied in Vitro.

Author information

1
Department of Applied Science, The College of William and Mary Williamsburg, VA, USA.

Abstract

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 (I(pump)), Na(+)-dependent K(+) current (I(K-Na)), and ATP-dependent K(+) current (I(K-ATP)). The pharmacological blockade of I(pump), I(K-Na), or I(K-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. I(pump), I(K-Na), and - to a lesser extent - I(K-ATP) contribute to terminating inspiratory bursts in the context of respiratory rhythm generation by responding to activity dependent cues such as Na(+) accumulation.

KEYWORDS:

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

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