title: Outward Currents Contributing to Inspiratory Burst Termination in preBötzinger Complex Neurons of Neonatal Mice Studied in Vitro.
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.
authors.affiliation: Department of Applied Science, The College of William and Mary Williamsburg, VA, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Krey
authors.forename: Adam M
authors.initials: AM
authors.lastname: Goodreau
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Arnold
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Del Negro