TASK channels contribute to the K+-dominated leak current regulating respiratory rhythm generation in vitro.
TASK channels contribute to the K+-dominated leak current regulating respiratory rhythm generation in vitro.
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DOI：
10.1523/jneurosci.4017-09.2010
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发表时间：
2010-03-24
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影响因子：
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通讯作者：
Smith JC
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文献类型：
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作者：
Koizumi H;Smerin SE;Yamanishi T;Moorjani BR;Zhang R;Smith JC
泄漏通道调节神经元的活动和兴奋性。确定神经元中存在哪些泄漏通道以及它们如何控制电生理行为是基础。在这里，我们研究了双孔结构域K+通道家族的成员，作为K+主导的漏导的一个组成部分，其控制和调节哺乳动物前BötC复合体（pre-BötC）中细胞和网络水平的节律产生，前BötC是延髓中神经元的兴奋性网络，与呼吸节律发生密切相关。通过对新生大鼠离体延髓脑片的前BötC神经元电流-电压（I-V）关系的电压钳分析，我们证明前BötC吸气神经元具有弱的外向整流总漏导，其逆转电位从K+平衡电位去极化约4 mV，表明背景K+通道是漏导的主要贡献者。该K+通道组分具有恒定场理论描述的I-V关系，电导被酸降低，并被挥发性麻醉剂氟烷增加，这些都是ASK的标志。我们通过单细胞RT-PCR确定，前BotC吸气神经元表达ASK-1，在某些情况下还表达ASK-3 mRNA。此外，酸去极化和增强的爆发频率的pre-BötC吸气神经元与内在的爆发属性。将酸化溶液微输注到有节奏活性的前BötC网络中增加了网络爆发频率，氟烷降低了爆发频率，酸逆转了氟烷的抑制作用，这与通过ASK通道调节网络活性一致。我们的结论是，TASK样通道在体外前Bötzinger复合体中呼吸节律产生的化学感受性调节中发挥重要作用。
Leak channels regulate neuronal activity and excitability. Determining which leak channels exist in neurons and how they control electrophysiological behavior is fundamental. Here we investigated TASK channels, members of the two-pore domain K+ channel family, as a component of the K+-dominated leak conductance that controls and modulates rhythm generation at cellular and network levels in the mammalian pre-Bötzinger complex (pre-BötC), an excitatory network of neurons in the medulla critically involved in respiratory rhythmogenesis. By voltage-clamp analyses of pre-BötC neuronal current-voltage (I-V) relations in neonatal rat medullary slices in vitro, we demonstrated that pre-BötC inspiratory neurons have a weakly outward-rectifying total leak conductance with reversal potential that was depolarized by ~4 mV from the K+ equilibrium potential, indicating that background K+ channels are dominant contributors to leak. This K+ channel component had I-V relations described by constant field theory, the conductance was reduced by acid and was augmented by the volatile anesthetic halothane, which are all hallmarks of TASK. We established by single-cell RT-PCR that pre-BotC inspiratory neurons express TASK-1 and in some cases also TASK-3 mRNA. Furthermore, acid depolarized and augmented bursting frequency of pre-BötC inspiratory neurons with intrinsic bursting properties. Microinfusion of acidified solutions into the rhythmically active pre-BötC network increased network bursting frequency, halothane decreased bursting frequency, and acid reversed the depressant effects of halothane, consistent with modulation of network activity by TASK channels. We conclude that TASK-like channels play a major functional role in chemosensory modulation of respiratory rhythm generation in the pre-Bötzinger complex in vitro.