Bayliss D A, Talley E M, Sirois J E, Lei Q
Department of Pharmacology, Health Sciences Center, University of Virginia, Box 448, Jordan Hall, Charlottesville, VA 22908, USA.
Respir Physiol. 2001 Dec;129(1-2):159-74. doi: 10.1016/s0034-5687(01)00288-2.
Central respiratory chemoreceptors adjust respiratory drive in a homeostatic response to alterations in brain pH and/or P(CO(2)). Multiple brainstem sites are proposed as neural substrates for central chemoreception, but molecular substrates that underlie chemosensitivity in respiratory neurons have not been identified. In rat brainstem neurons expressing transcripts for TASK-1, a two-pore domain K(+) channel, we characterized K(+) currents with kinetic and voltage-dependent properties identical to cloned rat TASK-1 currents. Native currents were sensitive to acid and alkaline shifts in the same physiological pH range as TASK-1 (pK approximately 7.4), and native and cloned pH-sensitive currents were modulated similarly by neurotransmitters and inhalational anesthetics. This pH-sensitive TASK-1 channel is an attractive candidate to mediate chemoreception because it is functionally expressed in respiratory-related neurons, including airway motoneurons and putative chemoreceptor neurons of locus coeruleus (LC). Inhibition of TASK-1 channels by extracellular acidosis can depolarize and increase excitability in those cells, thereby contributing to chemoreceptor function in LC neurons and directly enhancing respiratory motoneuronal output.
中枢呼吸化学感受器通过对脑内pH值和/或P(CO₂)变化的稳态反应来调节呼吸驱动。多个脑干部位被认为是中枢化学感受的神经基础，但尚未确定呼吸神经元中化学敏感性的分子基础。在表达TASK-1（一种双孔结构域钾通道）转录本的大鼠脑干神经元中，我们对钾电流进行了表征，其动力学和电压依赖性特性与克隆的大鼠TASK-1电流相同。天然电流在与TASK-1相同的生理pH范围内对酸和碱的变化敏感（pK约为7.4），并且天然和克隆的pH敏感电流受到神经递质和吸入性麻醉剂的类似调节。这种pH敏感的TASK-1通道是介导化学感受的一个有吸引力的候选者，因为它在与呼吸相关的神经元中功能性表达，包括气道运动神经元和蓝斑（LC）的假定化学感受神经元。细胞外酸中毒对TASK-1通道的抑制可使这些细胞去极化并增加兴奋性，从而有助于LC神经元的化学感受功能，并直接增强呼吸运动神经元的输出。
