Toppin Veronica A L, Harris Michael B, Kober Anna M, Leiter J C, St-John Walter M
Institute of Arctic Biology, University of Alaska Fairbanks, Alaska, USA.
J Appl Physiol (1985). 2007 Jul;103(1):220-7. doi: 10.1152/japplphysiol.00071.2007. Epub 2007 Apr 5.
In severe hypoxia or ischemia, normal eupneic breathing is replaced by gasping, which can serve as a powerful mechanism for "autoresuscitation." We have proposed that gasping is generated by medullary neurons having intrinsic pacemaker bursting properties dependent on a persistent sodium current. A number of neuromodulators, including serotonin, influence persistent sodium currents. Thus we hypothesized that endogenous serotonin is essential for gasping to be generated. To assess such a critical role for serotonin, a preparation of the perfused, juvenile in situ rat was used. Activities of the phrenic, hypoglossal, and vagal nerves were recorded. We added blockers of type 1 and/or type 2 classes of serotonergic receptors to the perfusate delivered to the preparation. Eupnea continued following additions of any of the blockers. Changes were limited to an increase in the frequency of phrenic bursts and a decline in peak heights of all neural activities. In ischemia, gasping was induced following any of the blockers. Few statistically significant changes in parameters of gasping were found. We thus did not find a differential suppression of gasping, compared with eupnea, following blockers of serotonin receptors. Such a differential suppression had been proposed based on findings using an in vitro preparation. We hypothesize that multiple neurotransmitters/neuromodulators influence medullary mechanisms underlying the neurogenesis of gasping. In greatly reduced in vitro preparations, the importance of any individual neuromodulator, such as serotonin, may be exaggerated compared with its role in more intact preparations.
在严重缺氧或缺血时,正常的平稳呼吸会被喘息所取代,喘息可作为一种强大的“自动复苏”机制。我们提出,喘息是由具有依赖持续性钠电流的内在起搏器爆发特性的延髓神经元产生的。包括5-羟色胺在内的多种神经调质会影响持续性钠电流。因此,我们假设内源性5-羟色胺对于产生喘息至关重要。为了评估5-羟色胺的这一关键作用,使用了灌注的幼年原位大鼠制备物。记录了膈神经、舌下神经和迷走神经的活动。我们将1型和/或2型5-羟色胺能受体阻滞剂添加到输送至该制备物的灌注液中。添加任何一种阻滞剂后,平稳呼吸仍持续。变化仅限于膈神经爆发频率增加以及所有神经活动的峰值高度下降。在缺血状态下,添加任何一种阻滞剂后都会诱发喘息。在喘息参数方面未发现统计学上的显著变化。因此,我们未发现与平稳呼吸相比,5-羟色胺受体阻滞剂对喘息有差异性抑制作用。基于使用体外制备物的研究结果曾提出过这种差异性抑制作用。我们假设多种神经递质/神经调质会影响喘息神经发生的延髓机制。在大大简化的体外制备物中,与在更完整的制备物中的作用相比,任何一种单独的神经调质(如5-羟色胺)的重要性可能被夸大了。