Dias Mirela B, Nucci Tatiane B, Margatho Lisandra O, Antunes-Rodrigues José, Gargaglioni Luciane H, Branco Luiz G S
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
J Appl Physiol (1985). 2007 Nov;103(5):1780-8. doi: 10.1152/japplphysiol.00424.2007. Epub 2007 Sep 6.
There is evidence that serotonin [5-hydroxytryptamine (5-HT)] is involved in the physiological responses to hypercapnia. Serotonergic neurons represent the major cell type (comprising 15-20% of the neurons) in raphe magnus nucleus (RMg), which is a medullary raphe nucleus. In the present study, we tested the hypothesis 1) that RMg plays a role in the ventilatory and thermal responses to hypercapnia, and 2) that RMg serotonergic neurons are involved in these responses. To this end, we microinjected 1) ibotenic acid to promote nonspecific lesioning of neurons in the RMg, or 2) anti-SERT-SAP (an immunotoxin that utilizes a monoclonal antibody to the third extracellular domain of the serotonin reuptake transporter) to specifically kill the serotonergic neurons in the RMg. Hypercapnia caused hyperventilation and hypothermia in all groups. RMg nonspecific lesions elicited a significant reduction of the ventilatory response to hypercapnia due to lower tidal volume (Vt) and respiratory frequency. Rats submitted to specific killing of RMg serotonergic neurons showed no consistent difference in ventilation during air breathing but had a decreased ventilatory response to CO(2) due to lower Vt. The hypercapnia-induced hypothermia was not affected by specific or nonspecific lesions of RMg serotonergic neurons. These data suggest that RMg serotonergic neurons do not participate in the tonic maintenance of ventilation during air breathing but contribute to the ventilatory response to CO(2). Ultimately, this nucleus may not be involved in the thermal responses to CO(2).
有证据表明，血清素[5-羟色胺（5-HT）]参与了对高碳酸血症的生理反应。血清素能神经元是延髓中缝大核（RMg）中的主要细胞类型（占神经元的15%-20%）。在本研究中，我们验证了两个假设：1）RMg在对高碳酸血症的通气和热反应中起作用；2）RMg血清素能神经元参与这些反应。为此，我们进行了微量注射：1）注射鹅膏蕈氨酸以促进RMg中神经元的非特异性损伤；2）注射抗血清素转运体单克隆抗体免疫毒素（anti-SERT-SAP）以特异性杀死RMg中的血清素能神经元。高碳酸血症在所有组中均引起了通气过度和体温过低。RMg的非特异性损伤导致由于潮气量（Vt）和呼吸频率降低，对高碳酸血症的通气反应显著降低。接受RMg血清素能神经元特异性杀伤的大鼠在空气呼吸时通气无一致差异，但由于Vt较低，对CO₂的通气反应降低。高碳酸血症诱导的体温过低不受RMg血清素能神经元特异性或非特异性损伤的影响。这些数据表明，RMg血清素能神经元不参与空气呼吸时通气的紧张性维持，但有助于对CO₂的通气反应。最终，该核团可能不参与对CO₂的热反应。
