Elsen Frank P, Ramirez Jan-Marino
Department of Pediatrics, The University of Chicago, Chicago, IL 60637, USA.
J Neurophysiol. 2005 Aug;94(2):1423-31. doi: 10.1152/jn.00237.2005. Epub 2005 May 11.
The mammalian respiratory network reorganizes during early postnatal life. We characterized the postnatal developmental changes of calcium currents in neurons of the pre-Bötzinger complex (pBC), the presumed site for respiratory rhythm generation. The pBC contains not only respiratory rhythmic (R) but also nonrhythmic neurons (nR). Both types of neurons express low- and high-voltage-activated (LVA and HVA) calcium currents. This raises the interesting issue: do calcium currents of the two co-localized neuron types have similar developmental profiles? To address this issue, we used the whole cell patch-clamp technique to compare in transverse slices of mice LVA and HVA calcium current amplitudes of the two neuron populations (R and nR) during the first and second postnatal week (P0-P16). The amplitude of HVA currents did not significantly change in R pBC-neurons (P0-P16), but it significantly increased in nR pBC-neurons during P8-P16. The dehydropyridine (DHP)-sensitive current amplitudes did not significantly change during the early postnatal development, suggesting that the observed amplitude changes in nR pBC-neurons are caused by (DHP) insensitive calcium currents. The ratio between HVA calcium current amplitudes dramatically changed during early postnatal development: At P0-P3, current amplitudes were significantly larger in R pBC-neurons, whereas at P8-P16, current amplitudes were significantly larger in nR pBC-neurons. Our results suggest that calcium currents in pBC neurons are differentially altered during postnatal development and that R pBC-neurons have fully expressed calcium currents early during postnatal development. This may be critical for stable respiratory rhythm generation in the underlying rhythm generating network.
哺乳动物的呼吸网络在出生后早期会进行重组。我们对前包钦格复合体(pBC)神经元中钙电流的出生后发育变化进行了表征,pBC被认为是呼吸节律产生的部位。pBC不仅包含呼吸节律性(R)神经元,还包含非节律性神经元(nR)。这两种类型的神经元都表达低电压激活(LVA)和高电压激活(HVA)钙电流。这就引出了一个有趣的问题:两种共定位的神经元类型的钙电流是否具有相似的发育模式?为了解决这个问题,我们使用全细胞膜片钳技术,比较了出生后第一周和第二周(P0 - P16)小鼠横向切片中两种神经元群体(R和nR)的LVA和HVA钙电流幅度。HVA电流幅度在R pBC神经元中(P0 - P16)没有显著变化,但在P8 - P16期间nR pBC神经元中显著增加。在出生后早期发育过程中,二氢吡啶(DHP)敏感电流幅度没有显著变化,这表明在nR pBC神经元中观察到的幅度变化是由(DHP)不敏感钙电流引起的。HVA钙电流幅度之间的比率在出生后早期发育过程中发生了显著变化:在P0 - P3时,R pBC神经元中的电流幅度显著更大,而在P8 - P16时,nR pBC神经元中的电流幅度显著更大。我们的结果表明,pBC神经元中的钙电流在出生后发育过程中发生了不同的变化,并且R pBC神经元在出生后发育早期就已经完全表达了钙电流。这对于基础节律产生网络中稳定的呼吸节律产生可能至关重要。