Developmental changes in the expression of GABAA receptor subunits α1, α2, and α3 in the rat pre-Botzinger complex
Developmental changes in the expression of GABAA receptor subunits α1, α2, and α3 in the rat pre-Botzinger complex
复制标题
DOI：
10.1152/japplphysiol.01264.2003
复制
发表时间：
2004-05-01
影响因子：
3.3
通讯作者：
Wong-Riley, MTT
中科院分区：
文献类型：
--
作者：
Liu, QL;Wong-Riley, MTT
以前，我们报告说，前Botzinger复合物（PBC）表现出显着降低细胞色素氧化酶活性在出生后第12天（P）。这与谷氨酸和NMDA受体亚基1的减少以及GABA、GABA（B）、甘氨酸受体和谷氨酸受体GluR 2的增加在时间上一致。为了验证我们的假设，即GABA（A）受体的各种α亚基在出生后发育过程中也会发生变化，就像它们在其他脑区一样，我们对P0至P21大鼠PBC中的GABA（A）受体亚基α 1，α 2和α 3进行了深入的免疫组织化学研究。结果表明：1）GABA（A）α 3-亚基在P0时表达水平较高，随年龄增长而下降，2）GABA（A）α 1-亚基在P0时表达水平较低，但随年龄增长而增加，3）α 1和α 3-亚基在P12时的发育趋势; GABA（A）α_2亚基在P0时表达量为中到轻度，在整个发育过程中表达量基本保持不变，P21时表达量最低。这些发现表明，在发育过程中α 3和α 1亚基相对表达的明显转换以及P12附近斜率的交叉可能与GABA（A）受体亚型的可能变化有关，这些变化将介导GABA传递的不同功能特性，例如主要是P12之前的抑制传递效率较低，而在P12及之后的抑制作用更成熟，如不同突触后电位的动力学所表明的。如前所述，这一机制可能部分导致P12时PBC内细胞色素氧化酶活性的急剧降低。
Previously, we reported that the pre-Botzinger complex (PBC) exhibited a dramatic reduction in cytochrome oxidase activity at postnatal day (P)12. This coincided in time with decreases in glutamate and NMDA receptor subunit 1 and increases in GABA, GABA(B), glycine receptor, and glutamate receptor GluR2. To test our hypothesis that various alpha-subunits of GABA(A) receptors also undergo changes in their expression during postnatal development, as they do in other brain regions, we undertook an in-depth immunohistochemical study of GABA(A) receptor subunits alpha1, alpha2, and alpha3 in the PBC of P0 to P21 rats. We found that 1) GABA(A) alpha3-subunit was expressed at relatively high levels at P0, which then declined with age; 2) GABA(A) alpha1-subunit was expressed at relatively low levels at P0 but increased with age; 3) the developmental trends of subunits alpha1 and alpha3 intersected at P12; and 4) GABA(A) alpha2-subunit expression was moderate to light at P0 and remained quite constant during development, being lowest at P21. These findings suggest that the apparent switch in relative expressions of subunits alpha3 and alpha1 during development and the intersection of slopes around P12 may be associated with possible changes in GABA(A) receptor subtypes that would mediate different functional properties of GABA transmission, such as primarily a less efficient inhibitory transmission before P12 and a more mature inhibitory effect at P12 and thereafter, as suggested by the kinetics of distinct postsynaptic potentials. This mechanism may contribute partially to the dramatic reduction in cytochrome oxidase activity within the PBC at P12, as shown previously.