Shaw P J, Charles S L, Salt T E
Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Brain Res. 1999 Jul 3;833(2):272-7. doi: 10.1016/s0006-8993(99)01556-5.
The diffusible intercellular messenger nitric oxide may have a modulatory role in the thalamus and this action may be mediated via activation of soluble guanylate cyclase. In order to investigate this possibility, we applied the cyclic-GMP analogue 8-Bromo-cyclic-GMP (8-Br-cGMP) onto neurones in the ventrobasal and lateral geniculate nuclei of the thalamus in anaesthetised rats, and compared its effects with those of a nitric oxide donor. 8-Br-cGMP enhanced the responses of neurones to iontophoretically applied NMDA and AMPA. Furthermore, somatosensory and visual responses of ventrobasal and lateral geniculate neurones were enhanced to 274+/-76% and 217+/-69% of control values, respectively. These effects were similar to those seen with nitric oxide donors in this study and previous work from this laboratory. When applied to thalamic neurones in an in vitro slice preparation, 8-Br-cGMP caused a membrane depolarisation associated with a decrease in input resistance. These findings indicate that activation of guanylate cyclase can cause a membrane depolarisation of thalamic neurones in vitro, and that this effect is sufficient to enhance action responses to ionotropic glutamate receptor stimulation via either exogenous agonists or sensory stimulation.
可扩散的细胞间信使一氧化氮可能在丘脑发挥调节作用，且该作用可能通过可溶性鸟苷酸环化酶的激活来介导。为了探究这种可能性，我们将环磷酸鸟苷类似物8-溴环磷酸鸟苷（8-Br-cGMP）应用于麻醉大鼠丘脑腹侧基底核和外侧膝状体核的神经元，并将其作用与一氧化氮供体的作用进行比较。8-Br-cGMP增强了神经元对离子电渗法施加的N-甲基-D-天冬氨酸（NMDA）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）的反应。此外，腹侧基底核和外侧膝状体神经元的体感和视觉反应分别增强至对照值的274±76%和217±69%。这些效应与本研究以及本实验室之前工作中一氧化氮供体所产生的效应相似。当将8-Br-cGMP应用于体外脑片制备中的丘脑神经元时，它会引起膜去极化并伴有输入电阻降低。这些发现表明，鸟苷酸环化酶的激活可在体外引起丘脑神经元的膜去极化，并且这种效应足以增强对离子型谷氨酸受体刺激（通过外源性激动剂或感觉刺激）的动作反应。
