Sodium channel alpha-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1): Different expression patterns in developing rat nervous system
Sodium channel alpha-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1): Different expression patterns in developing rat nervous system
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DOI：
10.1016/s0169-328x(96)00241-0
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发表时间：
1997-04-01
期刊：
影响因子：
--
通讯作者：
Waxman, SG
中科院分区：
文献类型：
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作者：
Felts, PA;Yokoyama, S;Waxman, SG
采用非同位素原位杂交细胞化学方法检测了发育期（E17-P30）海马、小脑、脊髓和背根神经节中钠通道α亚基mRNA I、II、III、NaG、Na 6和hNE（PN 1）的表达。结果显示，随着神经系统的成熟，每个钠通道mRNA的表达模式不同。在海马中，钠通道mRNA I在任何发育时间均未检测到，而mRNA II在E17和P30之间显示出增加的杂交信号。钠通道mRNA III在胚胎晚期和出生后早期更为普遍，在P30几乎检测不到。NaG的转录物在P2和P15之间显示瞬时表达，在E17以低水平表达，并且在P30不可检测。钠通道mRNA Na 6在E17和P15之间在海马结构中表现出高水平的表达，P30信号减弱。在海马中未检测到hNE（PN 1）mRNA。在小脑中，钠通道mRNA I在E17或P2时未检测到，但在P15时在浦肯野细胞中可检测到，并在P30时在这些细胞中继续显示低水平的表达。mRNA I在小脑颗粒细胞中的任何时间都没有检测到。钠通道mRNA II在发育中的小脑中表现出增加的表达，并且在P2开始的Purkinge细胞和P15的颗粒细胞中表现出增加的信号。钠通道mRNA III在小脑中随着发育而下调，尽管mRNA III在E17时很容易检测到，但在P15时在小脑的任何层中均未检测到。NaG mRNA在P2时表达最高，在E17和P15时表达较低，在P30时未检测到。Na 6 mRNA在E17小脑中高度表达;这种mRNA在整个发育过程中在浦肯野细胞中以高水平存在，尽管在颗粒细胞中，信号在P15-P30时减弱。钠通道hNE（PN 1）mRNA在小脑发育过程中均未检测到。在脊髓中，钠通道mRNA I在P2开始表达增加，并且在P30时高度表达，特别是在腹侧运动神经元中。在脊髓发育的各个阶段均检测到钠通道II mRNA;相反，在E17和P2检测到mRNA III，但在P30时表达水平非常低。NaG mRNA在P2时在脊髓中有短暂表达，但在E17和P30时未检测到。Na 6 mRNA在E17时表达水平很低，在P2时表达水平较高，在P15和P30时信号减弱，hNE（PN 1）mRNA在发育过程中的任何时候都未在脊髓中检测到。在背根神经节中，在P2时在DRG神经元中检测到钠通道I mRNA杂交信号，在P15和P30时水平略有增加。钠通道II mRNA表现出相对恒定的，中等水平的表达在所有发育年龄。钠通道III mRNA在E17时在DRG神经元中高度表达，但随着进一步发育而下调，因此P30检测不到。从E17到P30的所有发育阶段，部分DRG神经元均强烈表达NaG mRNA;一般而言，较大神经元的NaG标记水平高于较小神经元;随着发育，DRG神经元中Na 6 mRNA的表达逐渐增加;在E17，检测到低水平的Na 6 mRNA，而在P15到P30，部分神经元中存在高水平的Na 6 mRNA表达。hNE（PN 1）mRNA在P2时存在于DRG神经元中，并随着进一步发育而上调，使得到P30时hNE（PN 1）在所有大小的DRG神经元中表达。这些结果表明，钠通道α亚基mRNA I、II、III、NaG、Na 6和hNE（PN 1）在神经组织中表现出不同的时空表达模式，并提示钠通道Cu亚单位的表达受到差异调节。在P30 DRG中NaG和hNE（PN 1）mRNA的表达，而不是其他组织，可能提供了一个相关的存在，在背根神经节神经元，独特的钠电流。
The expression of sodium channel alpha-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1) was examined in developing (E17-P30) hippocampus, cerebellum, spinal cord and dorsal root ganglia using non-isotopic in situ hybridization cytochemistry. The results showed distinct patterns of expression for each of the sodium channel mRNAs with maturation of the nervous system. Tn the hippocampus, sodium channel mRNA I was not detected at any developmental time, while mRNA II showed increasing hybridization signal between E17 and P30. Sodium channel mRNA III was more prevalent at late embryonic and early postnatal times, and was barely detectable at P30. The transcript for NaG showed transient expression between P2 and P15, being expressed at low levels at E17 and not being detectable at P30. Sodium channel mRNA Na6 exhibited a high level of expression between E17 and P15 in the hippocampal formation, with an attenuation of the signal by P30. hNE (PN1) mRNA was not detected in the hippocampus at any time examined. In the cerebellum, sodium channel mRNA I was not detected at E17 or P2, but became detectable in Purkinje cells at P15 and continued to show a low level of expression in these cells at P30. mRNA I was not detected at any time examined in granule cells of the cerebellum. Sodium channel mRNA II exhibited increasing expression in the developing cerebellum and showed increasing signal in Purkinge cells beginning on P2 and granule cells on P15. Sodium channel mRNA III was down-regulated with development in the cerebellum, although mRNA III was readily detected at E17, it was not detected in any layers of the cerebellum by P15. NaG mRNA showed a peak of expression at P2, and was present at low levels at E17 and P15 and not detectable at P30. Na6 mRNA was highly expressed in the E17 cerebellum; this mRNA was present at high levels in Purkinje cells throughout development, although in granule cells the signal was attenuated at P15-P30. Sodium channel hNE (PN1) mRNA was not detected in the cerebellum at any time in development. In the spinal cord, sodium channel mRNA I showed increasing expression beginning at P2 and was highly expressed, particularly in ventral motor neurons, by P30. Sodium channel II mRNA was detected at all stages of development in the spinal cord; in contrast, mRNA III was detected at E17 and P2, but showed very low levels of expression by P30. NaG mRNA exhibited a transient expression in spinal cord at P2, but was not detectable at E17 and P30. Na6 mRNA was detectable at very low levels at E17 and became highly expressed at P2, prior to a reduction of the signal at P15 and P30, hNE (PN1) mRNA was not detected in the spinal cord at any time in development. In the dorsal root ganglia, sodium channel I mRNA hybridization signal was detected in DRG neurons at P2, with slightly increased levels at P15 and P30. Sodium channel II mRNA exhibited a relatively constant, moderate level of expression at all developmental ages. sodium channel III mRNA was highly expressed in DRG neurons at E17 but was down-regulated with further development so that it was not detectable by P30. NaG mRNA was strongly expressed by some DRG neurons at all stages of development from E17 to P30; in general the level of NaG labelling was greater in larger neurons than in smaller neurons.Na6 mRNA showed increasing expression with development in DRG neurons; at E17, low levels of Na6 mRNA were detected and by P15 to P30 high levels of expression were present in some neurons. hNE (PN1) mRNA was present in DRG neurons at P2, and was up-regulated with further development so that by P30 hNE (PN1) was expressed in all DRG neurons sizes.These results demonstrate that sodium channel alpha-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1) exhibit distinct spatial and temporal patterns of expression in nervous tissue, and suggest that the expression of the sodium channel cu-subunits is differentially regulated. The expression of NaG and hNE (PN1) mRNAs in P30 DRG, but not other tissues, may provide a correlate for the presence, in dorsal root ganglia neurons, of unique sodium currents.