Katchman A N, Hershkowitz N
Department of Neurology, Georgetown University Medical Center, Washington, D.C. 20007, USA.
Hippocampus. 1996;6(3):213-24. doi: 10.1002/(SICI)1098-1063(1996)6:3<213::AID-HIPO1>3.0.CO;2-O.
The role of the adenosine A1 receptor in the modulation of anoxia-induced synaptic glutamate release was examined in CA1 pyramidal neurons by whole-cell voltage-clamp recording in the rat hippocampal slice preparation. Anoxia leads to an increased action potential-independent synaptic glutamate release in the form of a higher frequency of miniature excitatory postsynaptic currents (mEPSCs). This increase is not significantly affected when slices are preincubated in the adenosine A1 receptor antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX). A second population of spontaneous inward currents, however, occurs in DPCPX-treated slices during a well-defined period following the onset of anoxia. Their suppression by glutamate antagonists, tetrodotoxin, or by the cutting of the Schaffer collateral pathway indicates that they represent action potential-dependent, glutamatergic excitatory postsynaptic currents (ap-EPSCs) originating from CA3 pyramidal neurons. CA3 neurons were examined in current-clamp whole-cell patch mode to determine the origin of this increased orthodromic excitation. After the onset of anoxia, CA3 cells initially exhibit a small depolarization or hyperpolarization associated with a decrease in input resistance. This is followed by transient depolarization (the depolarizing "nub"), which is associated with an increase in input resistance. The nub evoked single as well as bursts of action potentials in CA3 neurons. The occurrence of these CA3 nub-elicited action potentials coincides with that of ap-EPSCs recorded in the CA1 cells. Recording with cesium- rather than standard potassium-containing electrodes results in the suppression of the nub and its associated increase in input resistance. In conclusion we have shown that adenosine tone plays an important role in suppressing anoxia-induced spontaneous ap-EPSCs but not action potential-independent mEPSCs in CA1 neurons. These EPSCs originate from a depolarization in CA3 pyramidal neurons, which is associated with an increase in resistance. This previously undescribed phenomenon likely results from a decrease in the conductance of an unidentified potassium channel.
通过在大鼠海马脑片标本中进行全细胞电压钳记录，研究了腺苷A1受体在调节缺氧诱导的CA1锥体神经元突触谷氨酸释放中的作用。缺氧导致以更高频率的微小兴奋性突触后电流（mEPSCs）形式出现与动作电位无关的突触谷氨酸释放增加。当脑片在腺苷A1受体拮抗剂8-环戊基-1,3-二丙基黄嘌呤（DPCPX）中预孵育时，这种增加没有受到显著影响。然而，在缺氧开始后的一个明确时间段内，DPCPX处理的脑片中会出现第二批自发内向电流。谷氨酸拮抗剂、河豚毒素或切断Schaffer侧支通路对它们的抑制作用表明，它们代表源自CA3锥体神经元的动作电位依赖性谷氨酸能兴奋性突触后电流（ap-EPSCs）。在电流钳全细胞膜片模式下对CA3神经元进行检查，以确定这种增强的顺向兴奋的起源。缺氧开始后，CA3细胞最初表现出与输入电阻降低相关的小去极化或超极化。随后是短暂的去极化（去极化“核”），这与输入电阻增加有关。该“核”在CA3神经元中诱发单个动作电位以及动作电位爆发。这些由CA3“核”诱发的动作电位的出现与在CA1细胞中记录到的ap-EPSCs的出现一致。用铯电极而非标准含钾电极进行记录会导致“核”及其相关的输入电阻增加受到抑制。总之，我们已经表明，腺苷张力在抑制缺氧诱导的CA1神经元中自发的ap-EPSCs而非与动作电位无关的mEPSCs方面起重要作用。这些EPSCs源自CA3锥体神经元的去极化，这与电阻增加有关。这种先前未描述的现象可能是由于一种未确定的钾通道的电导降低所致。
