A neuronal mechanism of propofol-induced central respiratory depression in newborn rats
A neuronal mechanism of propofol-induced central respiratory depression in newborn rats
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DOI：
10.1213/01.ane.0000117226.45704.65
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发表时间：
2004-07-01
影响因子：
5.7
通讯作者：
Takeda, J
中科院分区：
文献类型：
--
作者：
Kashiwagi, M;Okada, Y;Takeda, J
异丙酚引起的中枢呼吸抑制的神经机制仍知之甚少。在本研究中，我们研究了这些机制以及γ-氨基丁酸（GABA）（A）受体在异丙酚诱导的中枢呼吸抑制中的参与。分离1至4日龄大鼠的脑干和颈脊髓，并用含氧人工脑脊液在体外维持制剂。从 C4 脊髓腹侧根记录节律性吸气爆发活动。使用穿孔膜片钳技术记录腹外侧延髓中呼吸神经元的活动。我们发现，洗澡时使用异丙酚会降低 C4 吸气爆发率，而使用 GABA(A) 拮抗剂荷包牡丹碱可以逆转这种情况。异丙酚引起静息膜电位超极化并抑制吸气前和呼气神经元动作电位的放电。相比之下，异丙酚对吸气神经元的静息膜电位和动作电位放电几乎没有影响。我们的研究结果表明，丙泊酚的抑郁作用至少部分是由丙泊酚对 GABA 受体的激动作用介导的。 GABA受体介导的吸气前神经元超极化很可能是异丙酚诱导新生大鼠呼吸抑制的神经元基础。
The neural mechanisms of propofol-induced central respiratory depression remain poorly understood. In the present study, we studied these mechanisms and the involvement of gamma-aminobutyric acid (GABA)(A) receptors in propofol-induced central respiratory depression. The brainstem and the cervical spinal cord of 1- to 4-day-old rats were isolated, and preparations were maintained in vitro with oxygenated artificial cerebrospinal fluid. Rhythmic inspiratory burst activity was recorded from the C4 spinal ventral root. The activity of respiratory neurons in the ventrolateral medulla was recorded using a perforated patch-clamp technique. We found that bath-applied propofol decreased C4 inspiratory burst rate, which could be reversed by the administration of a GABA(A) antagonist, bicuculline. Propofol caused resting membrane potentials to hyperpolarize and suppressed the firing of action potentials in preinspiratory and expiratory neurons. In contrast, propofol had little effect on resting membrane potentials and action potential firing in inspiratory neurons. Our findings suggest that the depressive effects of propofol are, at least in part, mediated by the agonistic action of propofol on GABA, receptors. It is likely that the GABA, receptor-mediated hyperpolarization of preinspiratory neurons serves as the neuronal basis of propofol-induced respiratory depression in the newborn rat.