Department of Applied Science, The College of William and Mary Williamsburg, VA, USA.
Front Neural Circuits. 2010 Nov 29;4:124. doi: 10.3389/fncir.2010.00124. eCollection 2010.
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.
我们研究了 PreBötzinger 复合体 (preBötC) 的吸气性中间神经元，以确定影响哺乳动物中枢模式发生器中爆发终止的细胞机制。保留 preBötC 神经元的新生小鼠切片在体外产生呼吸运动节律。与吸气相关的爆发依赖于内流的 Na(+)，因此与 Na(+)积累偶联的外向电流是协助或引起爆发终止的合理候选者。我们检查了 Na(+)/K(+) ATP 酶生电泵电流 (I(pump))、Na(+)依赖性 K(+)电流 (I(K-Na)) 和 ATP 依赖性 K(+)电流 (I(K-ATP))。I(pump)、I(K-Na)或 I(K-ATP)的药理学阻断会导致类似于不能终止的爆发的病理性去极化，从而阻碍呼吸节律的产生并可逆地停止运动输出。通过在突触分离的 preBötC 神经元中用电流阶跃命令模拟吸气性爆发，我们确定每种电流产生约 3-8mV 的短暂爆发后超极化，在 50-1600ms 内衰减。I(pump)、I(K-Na)，以及在较小程度上 - I(K-ATP)，通过响应 Na(+)积累等活动依赖性线索，有助于在呼吸节律产生的背景下终止吸气性爆发。
