Johnson Stephen M, Wiegel Liana M, Majewski David J
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive, Madison, WI 53706, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R901-10. doi: 10.1152/ajpregu.00912.2006. Epub 2007 May 23.
The role of pacemaker properties in vertebrate respiratory rhythm generation is not well understood. To address this question from a comparative perspective, brain stems from adult turtles were isolated in vitro, and respiratory motor bursts were recorded on hypoglossal (XII) nerve rootlets. The goal was to test whether burst frequency could be altered by conditions known to alter respiratory pacemaker neuron activity in mammals (e.g., increased bath KCl or blockade of specific inward currents). While bathed in artificial cerebrospinal fluid (aCSF), respiratory burst frequency was not correlated with changes in bath KCl (0.5-10.0 mM). Riluzole (50 microM; persistent Na(+) channel blocker) increased burst frequency by 31 +/- 5% (P < 0.05) and decreased burst amplitude by 42 +/- 4% (P < 0.05). In contrast, flufenamic acid (FFA, 20-500 microM; Ca(2+)-activated cation channel blocker) reduced and abolished burst frequency in a dose- and time-dependent manner (P < 0.05). During synaptic inhibition blockade with bicuculline (50 microM; GABA(A) channel blocker) and strychnine (50 muM; glycine receptor blocker), rhythmic motor activity persisted, and burst frequency was directly correlated with extracellular KCl (0.5-10.0 mM; P = 0.005). During synaptic inhibition blockade, riluzole (50 microM) did not alter burst frequency, whereas FFA (100 microM) abolished burst frequency (P < 0.05). These data are most consistent with the hypothesis that turtle respiratory rhythm generation requires Ca(2+)-activated cation channels but not pacemaker neurons, which thereby favors the group-pacemaker model. During synaptic inhibition blockade, however, the rhythm generator appears to be transformed into a pacemaker-driven network that requires Ca(2+)-activated cation channels.
起搏器特性在脊椎动物呼吸节律产生中的作用尚未得到充分理解。为了从比较的角度解决这个问题，将成年海龟的脑干在体外分离，并在舌下（XII）神经根上记录呼吸运动爆发。目的是测试爆发频率是否可以通过已知会改变哺乳动物呼吸起搏器神经元活动的条件来改变（例如，增加浴液KCl浓度或阻断特定内向电流）。当浸泡在人工脑脊液（aCSF）中时，呼吸爆发频率与浴液KCl（0.5 - 10.0 mM）的变化无关。利鲁唑（50 μM；持续性钠通道阻滞剂）使爆发频率增加31±5%（P < 0.05），并使爆发幅度降低42±4%（P < 0.05）。相反，氟芬那酸（FFA，20 - 500 μM；钙激活阳离子通道阻滞剂）以剂量和时间依赖性方式降低并消除爆发频率（P < 0.05）。在用荷包牡丹碱（50 μM；GABA(A)通道阻滞剂）和士的宁（50 μM；甘氨酸受体阻滞剂）进行突触抑制阻断期间，节律性运动活动持续存在，并且爆发频率与细胞外KCl（0.5 - 10.0 mM；P = 0.005）直接相关。在突触抑制阻断期间，利鲁唑（50 μM）没有改变爆发频率，而FFA（100 μM）消除了爆发频率（P < 0.05）。这些数据最符合这样的假设，即海龟呼吸节律的产生需要钙激活阳离子通道而不是起搏器神经元，因此支持群体起搏器模型。然而，在突触抑制阻断期间，节律发生器似乎转变为一个需要钙激活阳离子通道的起搏器驱动网络。
