Accorsi-Mendonça Daniela, Almado Carlos E L, Bonagamba Leni G H, Castania Jaci A, Moraes Davi J A, Machado Benedito H
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900Ribeirão Preto, SP, Brazil
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900Ribeirão Preto, SP, Brazil.
J Neurosci. 2015 Apr 29;35(17):6903-17. doi: 10.1523/JNEUROSCI.4598-14.2015.
Humans ascending to high altitudes are submitted to sustained hypoxia (SH), activating peripheral chemoreflex with several autonomic and respiratory responses. Here we analyzed the effect of short-term SH (24 h, FIO210%) on the processing of cardiovascular and respiratory reflexes using an in situ preparation of rats. SH increased both the sympatho-inhibitory and bradycardiac components of baroreflex and the sympathetic and respiratory responses of peripheral chemoreflex. Electrophysiological properties and synaptic transmission in the nucleus tractus solitarius (NTS) neurons, the first synaptic station of afferents of baroreflexes and chemoreflexes, were evaluated using brainstem slices and whole-cell patch-clamp. The second-order NTS neurons were identified by previous application of fluorescent tracer onto carotid body for chemoreceptor afferents or onto aortic depressor nerve for baroreceptor afferents. SH increased the intrinsic excitability of NTS neurons. Delayed excitation, caused by A-type potassium current (IKA), was observed in most of NTS neurons from control rats. The IKA amplitude was higher in identified second-order NTS neurons from control than in SH rats. SH also blunted the astrocytic inhibition of IKA in NTS neurons and increased the synaptic transmission in response to afferent fibers stimulation. The frequency of spontaneous excitatory currents was also increased in neurons from SH rats, indicating that SH increased the neurotransmission by presynaptic mechanisms. Therefore, short-term SH changed the glia-neuron interaction, increasing the excitability and excitatory transmission of NTS neurons, which may contribute to the observed increase in the reflex sensitivity of baroreflex and chemoreflex in in situ preparation.
人类上升到高海拔地区会经历持续性缺氧(SH),从而激活外周化学反射并引发多种自主神经和呼吸反应。在此,我们使用大鼠原位制备模型分析了短期SH(24小时,FIO2 10%)对心血管和呼吸反射处理的影响。SH增加了压力反射的交感抑制和心动过缓成分以及外周化学反射的交感和呼吸反应。使用脑干切片和全细胞膜片钳评估了孤束核(NTS)神经元的电生理特性和突触传递,NTS神经元是压力反射和化学反射传入神经的第一个突触站。通过先前将荧光示踪剂应用于颈动脉体以标记化学感受器传入神经或应用于主动脉减压神经以标记压力感受器传入神经来识别二阶NTS神经元。SH增加了NTS神经元的内在兴奋性。在大多数对照大鼠的NTS神经元中观察到由A型钾电流(IKA)引起的延迟兴奋。对照大鼠中已识别的二阶NTS神经元的IKA幅度高于SH大鼠。SH还减弱了NTS神经元中星形胶质细胞对IKA的抑制作用,并增加了对传入纤维刺激的突触传递。SH大鼠神经元中自发兴奋性电流的频率也增加,表明SH通过突触前机制增加了神经传递。因此,短期SH改变了神经胶质细胞与神经元之间的相互作用,增加了NTS神经元的兴奋性和兴奋性传递,这可能有助于在原位制备模型中观察到的压力反射和化学反射反射敏感性增加。