首页> 外文期刊>Frontiers in Physiology >Excitatory Modulation of the preB?tzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide
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Excitatory Modulation of the preB?tzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide

机译:内源性硫化氢对PreB?tzinger复杂吸气节律发生网络的兴奋性调节

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Hydrogen Sulfide (H_(2)S) is one of three gasotransmitters that modulate excitability in the CNS. Global application of H_(2)S donors or inhibitors of H_(2)S synthesis to the respiratory network has suggested that inspiratory rhythm is modulated by exogenous and endogenous H_(2)S. However, effects have been variable, which may reflect that the RTN/pFRG (retrotrapezoid nucleus, parafacial respiratory group) and the preB?tzinger Complex (preB?tC, critical for inspiratory rhythm generation) are differentially modulated by exogenous H_(2)S. Importantly, site-specific modulation of respiratory nuclei by H_(2)S means that targeted, rather than global, manipulation of respiratory nuclei is required to understand the role of H_(2)S signaling in respiratory control. Thus, our aim was to test whether endogenous H_(2)S, which is produced by cystathionine-β-synthase (CBS) in the CNS, acts specifically within the preB?tC to modulate inspiratory activity under basal ( in vitro / in vivo ) and hypoxic conditions ( in vivo ). Inhibition of endogenous H_(2)S production by bath application of the CBS inhibitor, aminooxyacetic acid (AOAA, 0.1–1.0 mM) to rhythmic brainstem spinal cord (BSSC) and medullary slice preparations from newborn rats, or local application of AOAA into the preB?tC (slices only) caused a dose-dependent decrease in burst frequency. Unilateral injection of AOAA into the preB?tC of anesthetized, paralyzed adult rats decreased basal inspiratory burst frequency, amplitude and ventilatory output. AOAA in vivo did not affect the initial hypoxia-induced (10% O_(2), 5 min) increase in ventilatory output, but enhanced the secondary hypoxic respiratory depression. These data suggest that the preB?tC inspiratory network receives tonic excitatory modulation from the CBS-H_(2)S system, and that endogenous H_(2)S attenuates the secondary hypoxic respiratory depression.
机译:硫化氢(H_(2)S)是调节CNS兴奋性的三种气体递质之一。 H_(2)S供体或H_(2)S合成抑制剂在呼吸网络中的全球应用表明,吸气节律受外源性和内源性H_(2)S调节。然而,效果是可变的,这可能反映出RTN / pFRG(梯形核,面下呼吸群)和preB?tzinger复合体(preB?tC,对呼吸节奏的形成至关重要)受到外源性H_(2)S的差异调节。重要的是,H_(2)S对呼吸核的位点特异性调节意味着需要有针对性的而不是整体的呼吸核操纵才能了解H_(2)S信号在呼吸控制中的作用。因此,我们的目的是测试中枢神经系统中胱硫醚-β-合酶(CBS)产生的内源性H_(2)S是否在preB?tC内特异性地调节基础(体外/体内)下的吸气活性)和低氧条件(体内)。通过将CBS抑制剂氨氧基乙酸(AOAA,0.1–1.0 mM)浸入有节律的脑干脊髓(BSSC)和新生大鼠的髓样切片制剂中或局部应用AOAA抑制内源性H_(2)S的产生preB?tC(仅切片)导致猝发频率剂量依赖性降低。在麻醉,瘫痪的成年大鼠的preB?tC中单侧注射AOAA会降低基础吸气爆发频率,幅度和通气量。体内的AOAA不会影响最初的低氧诱导的通气量增加(10%O_(2),5分钟),但会增强继发的低氧呼吸抑制。这些数据表明,preB?tC吸气网络从CBS-H_(2)S系统接受了补品兴奋性调制,而内源性H_(2)S减轻了继发性低氧性呼吸抑制。

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