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

We studied pre-Botzinger(preBotC) inspiratory interneurons to determine the cellular mechanisms that influence burst termination in a mammalian central pattern generator. Neonatal mouse slice preparations that retain pre-BoTC 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, 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 preBoTC 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