Solomon Irene C, Chon Ki H, Rodriguez Melissa N
Department of Physiology and Biophysics, State University of New York, Stony Brook 11794-8661, USA.
J Neurophysiol. 2003 Jan;89(1):135-49. doi: 10.1152/jn.00697.2002.
Recent investigations have examined the influence of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in vitro using transverse medullary slice and en bloc brain stem-spinal cord preparations obtained from neonatal (1-5 days postnatal) mice. Gap junction proteins, however, have been identified in both neurons and glia in brain stem regions implicated in respiratory control in both neonatal and adult rodents. Here, we used an in vitro arterially perfused rat preparation to examine the role of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in adult rodents. We recorded rhythmic inspiratory motor activity from one or both phrenic nerves before and during pharmacological blockade (i.e., uncoupling) of brain stem gap junctions using carbenoxolone (100 microM), 18alpha-glycyrrhetinic acid (25-100 microM), 18beta-glycyrrhetinic acid (25-100 microM), octanol (200-300 microM), or heptanol (200 microM). During perfusion with a gap junction uncoupling agent, we observed an increase in the frequency of phrenic bursts (~95% above baseline frequency; P < 0.001) and a decrease in peak amplitude of integrated phrenic nerve discharge (P < 0.001). The increase in frequency of phrenic bursts resulted from a decrease in both T(I) (P < 0.01) and T(E) (P < 0.01). In addition, the pattern of phrenic nerve discharge shifted from an augmenting discharge pattern to a "bell-shaped" or square-wave discharge pattern in most experiments. Spectral analyses using a fast Fourier transform (FFT) algorithm revealed a reduction in the peak power of both the 40- to 50-Hz peak (corresponding to the MFO) and 90- to 110-Hz peak (corresponding to the HFO) although spurious higher frequency activity (> or =130 Hz) was observed, suggesting an overall loss or reduction in inspiratory-phase synchronization. Although additional experiments are required to identify the specific brain stem regions and cell types (i.e., neurons, glia) mediating the observed modulations in phrenic motor output, these findings suggest that gap junction communication modulates generation of respiratory rhythm and inspiratory motoneuron synchronization in adult rodents in vitro.
最近的研究使用从新生（出生后1 - 5天）小鼠获得的横断延髓切片和整体脑干 - 脊髓标本，在体外研究了缝隙连接通讯对呼吸节律的产生和调节以及吸气运动神经元同步化的影响。然而，在新生和成年啮齿动物中，与呼吸控制相关的脑干区域的神经元和胶质细胞中均已鉴定出缝隙连接蛋白。在此，我们使用体外动脉灌注大鼠标本，研究缝隙连接通讯在成年啮齿动物中对呼吸节律的产生和调节以及吸气运动神经元同步化的作用。我们在使用羧苄青霉素（100微摩尔）、18α - 甘草次酸（25 - 100微摩尔）、18β - 甘草次酸（25 - 100微摩尔）、辛醇（200 - 300微摩尔）或庚醇（200微摩尔）对脑干缝隙连接进行药理学阻断（即解偶联）之前和期间，记录一侧或双侧膈神经的节律性吸气运动活动。在用缝隙连接解偶联剂灌注期间，我们观察到膈神经冲动频率增加（比基线频率高约95%；P < 0.001），膈神经放电积分峰值幅度降低（P < 0.001）。膈神经冲动频率的增加是由于吸气时间（T(I)）（P < 0.01）和呼气时间（T(E)）（P < 0.01）均缩短所致。此外，在大多数实验中，膈神经放电模式从递增放电模式转变为“钟形”或方波放电模式。使用快速傅里叶变换（FFT）算法进行的频谱分析显示，40至50赫兹峰值（对应于平均频率振荡）和90至110赫兹峰值（对应于高频振荡）的峰值功率均降低，尽管观察到了虚假的更高频率活动（≥130赫兹），这表明吸气相同步性总体丧失或降低。尽管需要额外的实验来确定介导所观察到的膈神经运动输出调节的特定脑干区域和细胞类型（即神经元、胶质细胞），但这些发现表明缝隙连接通讯在体外调节成年啮齿动物的呼吸节律产生和吸气运动神经元同步化。
