Dong X W, Feldman J L
Department of Physiological Science, University of California Los Angeles 90095-1527, USA.
J Neurosci. 1995 May;15(5 Pt 1):3458-67. doi: 10.1523/JNEUROSCI.15-05-03458.1995.
The involvement and mechanisms of adenosine A1 receptors in regulating bulbospinal synaptic transmission of inspiratory drive to phrenic motoneurons were investigated. The adenosine analog N6-cyclopentyladenosine (CPA) induced a dose-dependent decrease of both inspiratory-modulated activity of C4 ventral roots and synaptic currents of phrenic motoneurons in an in vitro brainstem/spinal cord preparation from neonatal rats. No significant changes were observed in steady-state membrane current (during the expiratory phase). The depressant action of CPA on inspiratory drive was blocked by the selective A1 receptor antagonist 8-cyclopentyltheophylline (CPT). The adenosine receptor antagonist 3-isobutyl-1-methylxanthine (IBMX) induced varying degrees of enhancement of inspiratory-modulated synaptic current, as did CPT. This suggests a role of endogenous adenosine in synaptic transmission of respiratory drive to phrenic motoneurons. The relative contribution of pre- and postsynaptic adenosine receptors was examined by looking at the effects of CPA on postsynaptic membrane properties and on spontaneous or miniature excitatory postsynaptic currents (EPSCs). CPA had no detectable effect on the input resistance of phrenic moto-neurons. Moreover, the inward currents of phrenic moto-neurons in response to exogenously applied glutamate were not affected by adenosine-related compounds. On the other hand, CPA produced a significant decrease in the frequency of spontaneous and of miniature EPSCs. We conclude that adenosine can modulate transmission of inspiratory drive from bulbospinal neurons to phrenic motoneurons via presynaptic A1 receptors.
研究了腺苷A1受体在调节延髓脊髓向膈运动神经元的吸气驱动突触传递中的作用及机制。在新生大鼠体外脑干/脊髓标本中，腺苷类似物N6-环戊基腺苷（CPA）引起C4腹根吸气调制活动和膈运动神经元突触电流呈剂量依赖性降低。在稳态膜电流（呼气期）未观察到显著变化。CPA对吸气驱动的抑制作用被选择性A1受体拮抗剂8-环戊基茶碱（CPT）阻断。腺苷受体拮抗剂3-异丁基-1-甲基黄嘌呤（IBMX）和CPT一样，可引起吸气调制突触电流不同程度的增强。这表明内源性腺苷在呼吸驱动向膈运动神经元的突触传递中起作用。通过观察CPA对突触后膜特性以及对自发或微小兴奋性突触后电流（EPSC）的影响，研究了突触前和突触后腺苷受体的相对贡献。CPA对膈运动神经元的输入电阻没有可检测到的影响。此外，外源性应用谷氨酸后膈运动神经元的内向电流不受腺苷相关化合物的影响。另一方面，CPA使自发和微小EPSC的频率显著降低。我们得出结论，腺苷可通过突触前A1受体调节从延髓脊髓神经元到膈运动神经元的吸气驱动传递。
