Ictal epileptiform activity in the CA3 region of hippocampal slices produced by pilocarpine.
Ictal epileptiform activity in the CA3 region of hippocampal slices produced by pilocarpine.
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毛果芸香碱产生的海马切片 CA3 区的发作性癫痫样活动。
DOI：
10.1152/jn.1998.79.6.3019
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Yang,Y
中科院分区：
文献类型：
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作者：
Rutecki,PA;Yang,Y
[2]鲁特基，保罗.杨伊丽.匹罗卡品诱导的大鼠海马脑片CA3区癫痫样放电.神经生理学杂志，79：3019-3029,1998.匹罗卡品是一种毒碱激动剂，会产生癫痫持续状态，与慢性复发性癫痫的后期发展有关。将匹罗卡品(10μM)应用于大鼠海马片，可产生类似于癫痫发作间歇活动的短暂(<；200ms)癫痫样放电，以及持续数秒(3-20 S)的更长时间的同步神经元激活，与发作期或癫痫样放电相当。我们评估了有利于发作期活动模式的因素，并确定了发作期放电的生物物理性质。当细胞外钾([K+]o)从5 mM增加到7.5 mM时，观察到发作性放电的概率增加。[K+]升高至10 mm时，癫痫发作模式消失，34个脑片中有20个出现癫痫样活动的去同步化。使人工脑脊液(ACSF)处于低渗状态有利于5 mm[K+]o的发作放电，但使7.5 mm[K+]o ACSF模式转变为发作间期放电或去同步化活动。相反，增加渗透压抑制了发作模式。M受体拮抗剂阿托品(1μM，n=5)和哌仑西平(1μM，n=6)可阻断匹罗卡品诱发的发作放电。Kainate/α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic酸受体阻断使所有癫痫样活动停止(n=8)。甲基-D-天冬氨酸拮抗剂L(100μM，n=34)不改变癫痫样放电模式，但显著增加发作间期放电频率，延长发作间期放电时间。发作放电的细胞内特征是与动作电位产生相关的去极化，并以4-10赫兹的膜振荡持续存在。电流钳记录−为2 2.7±2.2 mV(n=11)，电压钳记录−为2 0.9±3.1 mV(n=7)。在γ-氨基丁酸-A阻断剂荷包牡丹碱(10μM，n=6)存在下，发作间期放电的逆转电位为−2.2±2.6 mV，与未加荷包牡丹碱时相比有显著差异。加入7.5 mM[K+]和10μM匹罗卡品的荷包牡丹碱不能引起癫痫样放电模式的改变，但可显著增加发作间期放电频率，延长发作放电时程。突触和非突触机制对癫痫样活动发作模式的产生都很重要。虽然匹罗卡品产生的同步癫痫样活动需要快速的谷氨酸介导的突触传递，但从发作间期到发作的活动模式的转换依赖于[K+]O，并可能受到细胞外空间的影响。
Rutecki, Paul A. and Yili Yang.Ictal epileptiform activity in the CA3 region of hippocampal slices produced by pilocarpine.J. Neurophysiol.79: 3019–3029, 1998. Pilocarpine, a muscarinic agonist, produces status epilepticus that is associated with the later development of chronic recurrent seizures. When applied to rat hippocampal slices, pilocarpine (10 μM) produced brief (<200 ms) epileptiform discharges that resembled interictal activity that occurs between seizures, as well as more prolonged synchronous neuronal activation that lasted seconds (3–20 s), and was comparable to ictal or seizures-like discharges. We assessed the factors that favored ictal patterns of activity and determined the biophysical properties of the ictal discharge. The probability of observing ictal discharges was increased when extracellular potassium ([K+]o) was increased from 5 to 7.5 mM. Raising [K+]oto 10 mM resulted in loss of ictal patterns and, in 20 of 34 slices, desynchronization of epileptiform activity. Making the artificial cerebrospinal fluid (ACSF) hyposmotic favored ictal discharges at 5 mM [K+]o, but shifted 7.5 mM [K+]oACSF patterns to interictal discharges or desynchronized activity. Conversely, increasing osmolality suppressed ictal patterns. The pilocarpine-induced ictal discharges were blocked by atropine (1 μM,n= 5), a muscarinic antagonist, and pirenzepine (1 μM,n= 6), a selective M1receptor antagonist. Kainate/α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor blockade stopped all epileptiform activity (n= 8). TheN-methyl-d-aspartate antagonistd,l-2-amino-5-phosphonovaleric acid (100 μM,n= 34) did not change the pattern of epileptiform activity but significantly increased the rate of interictal discharges and prolonged the duration of ictal discharges. The ictal discharge was characterized intracellularly by a depolarization that was associated with action potential generation and persisted as a membrane oscillation of 4–10 Hz. The ictal oscillations reversed in polarity at −22.7 ± 2.2 mV (n= 11) with current-clamp recordings and −20.9 ± 3.1 mV (n= 7) with voltage-clamp recordings. The reversal potential of the ictal discharge in the presence of the γ-aminobutyric acid-A blocker bicuculline (10 μM,n= 6) was −2.2 ± 2.6 mV and was significantly different from that measured without bicuculline. Bicuculline added to 7.5 mM [K+]oand 10 μM pilocarpine did not cause epileptiform activity to change pattern but significantly increased the rate of interictal discharges and prolonged the ictal discharge duration. Both synaptic and nonsynaptic mechanisms are important for the generation of ictal patterns of epileptiform activity. Although the synchronous epileptiform activity produced by pilocarpine required fast glutamate-mediated synaptic transmission, the transition from an interictal to ictal pattern of activity depended on [K+]oand could be influenced by extracellular space.