Solomon I C, Halat T J, El-Maghrabi R, O'Neal M H
Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, New York 11794-8661, USA.
J Comp Neurol. 2001 Nov 5;440(1):12-9. doi: 10.1002/cne.1366.
The pre-Bötzinger complex (pre-BötC) is hypothesized to be the site for respiratory rhythm generation in mammals. Studies examining the cellular mechanisms mediating rhythm generation have focused on the role of chemically mediated synaptic interactions; however, electrotonic synaptic interactions (i.e., electrotonic coupling), which occur by means of gap junctions, may also play a role. Here, we used immunoblot and immunohistochemical analyses to determine whether the pre-BötC contains the gap junction proteins necessary for electrotonic communication and whether the presence and distribution of these gap junction proteins show a developmental change in expression. We found that both connexin26 (Cx26) and connexin32 (Cx32) were expressed in pre-BötC neurons of neonatal and adult rats; however, the relative amounts and their distribution varied by age. Cx26 labeling was seen in a high proportion of pre-BötC neurons in neonatal rats < or = 7 days postnatal (P7) but declined with increasing age. In contrast, Cx32 labeling was sparse in pre-BötC neurons of neonatal rats < or = P7, but increased with increasing age; the highest proportion was seen in adult rats. These data suggest the potential for gap junctional communication in the pre-BötC of both neonatal and adult rats, and we propose that the gap junction proteins Cx26 and Cx32 form the neuroanatomic substrate for this gap junctional communication, which may be important in the synchronization of neural activity generating respiratory rhythm.
前包钦格复合体(pre-BötC)被认为是哺乳动物呼吸节律产生的部位。研究介导节律产生的细胞机制主要集中在化学介导的突触相互作用的作用上;然而,通过缝隙连接发生的电突触相互作用(即电耦合)也可能起作用。在这里,我们使用免疫印迹和免疫组织化学分析来确定前包钦格复合体是否包含电通信所需的缝隙连接蛋白,以及这些缝隙连接蛋白的存在和分布是否显示出发育过程中的表达变化。我们发现,连接蛋白26(Cx26)和连接蛋白32(Cx32)在新生和成年大鼠的前包钦格复合体神经元中均有表达;然而,其相对含量及其分布随年龄而变化。在出生后≤7天(P7)的新生大鼠中,高比例的前包钦格复合体神经元可见Cx26标记,但随着年龄增长而下降。相反,在≤P7的新生大鼠的前包钦格复合体神经元中,Cx32标记稀疏,但随年龄增长而增加;在成年大鼠中比例最高。这些数据表明新生和成年大鼠的前包钦格复合体中存在缝隙连接通信的潜力,并且我们提出缝隙连接蛋白Cx26和Cx32形成了这种缝隙连接通信的神经解剖学基础,这可能在产生呼吸节律的神经活动同步中起重要作用。