Quinine, a blocker of neuronal Cx36 channels, suppresses seizure activity in rat neocortex in vivo
Quinine, a blocker of neuronal Cx36 channels, suppresses seizure activity in rat neocortex in vivo
复制标题
DOI：
10.1111/j.1528-1167.2005.00254.x
复制
发表时间：
2005-10-01
期刊：
影响因子：
5.6
通讯作者：
Szente, M
中科院分区：
文献类型：
--
作者：
Gajda, Z;Szupera, Z;Szente, M
目的：采用4-氨基吡啶在体癫痫模型，采用药理学方法研究了通过连接蛋白36 （Cx36）通道的神经元间隙连接（GJ）通讯在主灶和镜像灶中对癫痫发生和癫痫维持和传播的选择性贡献。方法：对麻醉的成年大鼠进行ECoG记录，在诱导前或已经活动的癫痫灶局部应用奎宁、选择性Cx36阻滞剂或广谱GJ阻滞剂卡贝诺洛酮和辛醇。结果：在诱导癫痫样活动前，奎宁阻断Cx36通道可轻微降低癫痫发生。当奎宁在25-30次重复发作后应用时，在癫痫发作开始时出现频率为bb0 - 15hz的新放电模式。尽管癫痫发作次数增加，但由于癫痫发作持续时间显著缩短，总癫痫活动减少。除频率为11-12 Hz的癫痫发作放电外，所有模式的癫痫发作放电幅度均下降。Cx36通道的阻断和GJ通道的全面阻断导致了胚胎形成过程中不同性质的改变。结论：阻断已激活的癫痫灶Cx36通道具有抗惊厥作用，可改变1 ~ 18hz癫痫发作放电的表现。我们的研究结果表明，通过Cx36通道的GJ通信不同地参与了产生不同频率癫痫发作放电的网络活动的同步。此外，我们得出结论，在成年大鼠新皮层中，神经元和胶质GJ通讯都有助于癫痫发作的表现和传播。
Purpose: The selective contribution of neuronal gap junction (GJ) communication via connexin 36 (Cx36) channels to epileptogenesis and to the maintenance and propagation of seizures was investigated in both the primary focus and the mirror focus by using pharmacologic approaches with the 4-aminopyridine in vivo epilepsy model.Methods: ECoG recording was performed on anesthetized adult rats, in which either quinine, a selective blocker of Cx36, or the broad-spectrum GJ blockers carbenoxolone and octanol were applied locally, before the induction or at already active epileptic foci.Results: The blockade of Cx36 channels by quinine before the induction of epileptiform activity slightly reduced the epileptogenesis. When quinine was applied after 25-30 repetitions of seizures, a new discharge pattern appeared with frequencies > 15 Hz at the initiation of seizures. In spite of the increased number of seizures, the summated ictal activity decreased, because of the significant reduction in the duration of the seizures. The amplitudes of the seizure discharges of all the patterns decreased, with the exception of those with frequencies of 11-12 Hz. The blockade of Cx36 channels and the global blockade of the GJ channels resulted in qualitatively different modifications in ictogenesis.Conclusions: The blockade of Cx36 channels at the already active epileptic focus has an anticonvulsive effect and modifies the manifestation of the 1- to 18-Hz seizure discharges. Our findings indicate that the GJ communication via Cx36 channels is differently involved in the synchronization of the activities of the networks generating seizure discharges with different frequencies. Additionally, we conclude that both neuronal and glial GJ communication contribute to the manifestation and propagation of seizures in the adult rat neocortex.