Li H, Henry J L
Departments of Psychiatry and Physiology, 3655 Drummond St., McGill University, H3G 1Y6, Montreal, QC, Canada.
Eur J Pharmacol. 2000 Nov 3;407(3):237-44. doi: 10.1016/s0014-2999(00)00661-0.
To investigate the action of adenosine on interneurons as well as on excitatory synaptic transmission onto interneurons in the hippocampus, intracellular recordings were made from electrophysiologically identified interneurons in the CA1 region of the hippocampal slice in vitro. The effects of adenosine and the preferential adenosine A1 receptor agonist, chloroadenosine, were examined. Application of 50 microM adenosine and 20 microM chloroadenosine to the bath produced a hyperpolarization of 5.6+/-1.6 (n=5) and 6.1+/-1.4 mV (n=6), respectively, as well as a decrease in membrane input resistance of 18.1+/-3.5% (n=5) and 18.5+/-1.4% (n=6), respectively. Adenosine depressed the postsynaptic potentials (PSPs) elicited in the interneurons by stimulation of Schaffer collateral fibers by 73+/-6.8% (n=5). The amplitude and the duration of the afterhyperpolarization which followed the spike of the action potential were attenuated by 48+/-6.9% and 31+/-8.6%, respectively (n=5). Chloroadenosine depressed the evoked PSPs in these interneurons by 61.2+/-2.7% (n=6) and depressed the duration and the amplitude of the afterhyperpolarization by 85.2+/-4.5% and by 72.6+/-4.8%, respectively (n=6). The data show that adenosine and chloroadenosine directly inhibit hippocampal CA1 interneurons by blocking the synaptic input, by hyperpolarizing the membrane potential and by depressing the afterhyperpolarization following individual action potential spikes. It is proposed that adenosine A1 receptors are present at pre- and/or postsynaptic sites of interneuron synapses in the hippocampal CA1 region. The present findings demonstrate that adenosine A1 receptor activation in CA1 interneurons is able to modulate the excitatory synaptic input to, and excitability of, these neurons. Thus, as adenosine is released during ischemia and epilepsy, adenosine may protect both interneurons and pyramidal cells from glutamate excitotoxicity through activation of adenosine A1 receptors on these neurons in the hippocampus.
为了研究腺苷对海马中间神经元的作用以及对中间神经元兴奋性突触传递的影响，在体外海马脑片CA1区对经电生理鉴定的中间神经元进行细胞内记录。检测了腺苷和选择性腺苷A1受体激动剂氯腺苷的作用。向浴槽中加入50微摩尔的腺苷和20微摩尔的氯腺苷，分别使膜电位超极化5.6±1.6毫伏（n = 5）和6.1±1.4毫伏（n = 6），同时膜输入电阻分别降低18.1±3.5%（n = 5）和18.5±1.4%（n = 6）。腺苷使刺激海马伞侧支纤维在中间神经元诱发的突触后电位（PSP）降低73±6.8%（n = 5）。动作电位锋电位后的超极化后电位的幅度和持续时间分别降低48±6.9%和31±8.6%（n = 5）。氯腺苷使这些中间神经元中诱发的PSP降低61.2±2.7%（n = 6），并使超极化后电位的持续时间和幅度分别降低85.2±4.5%和72.6±4.8%（n = 6）。数据表明，腺苷和氯腺苷通过阻断突触输入、使膜电位超极化以及抑制单个动作电位锋电位后的超极化后电位，直接抑制海马CA1中间神经元。有人提出，腺苷A1受体存在于海马CA1区中间神经元突触的突触前和/或突触后部位。目前的研究结果表明，CA1中间神经元中腺苷A1受体的激活能够调节这些神经元的兴奋性突触输入和兴奋性。因此，由于腺苷在缺血和癫痫发作期间释放，腺苷可能通过激活海马中这些神经元上的腺苷A1受体，保护中间神经元和锥体细胞免受谷氨酸兴奋性毒性的影响。
