Mohammadi Bahram, Krampfl Klaus, Cetinkaya Cener, Wolfes Heiner, Dengler Reinhard, Bufler Johannes
Department of Neurology, Medical University Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Pharmacol Res. 2005 Jun;51(6):587-92. doi: 10.1016/j.phrs.2005.02.021.
Glycine receptor channels are pentameric ligand-gated ion channels that respond to the application of inhibitory neurotransmitters by opening of a chloride-selective central pore. Topiramate (TPM) is a broad-spectrum antiepileptic drug used as add-on or monotherapy for focal seizures. In the present study the interaction of TPM with glycine receptor channels was studied on outside-out patches from HEK293 cells expressing alpha1beta glycine receptor channels. The patch clamp techniques combined with ultra fast solution exchange enabled us to investigate the kinetics of receptor channels in presence of TPM. Our study showed no agonistic or potentiating effect for TPM on glycine receptor channels. However, in presence of 1 mM glycine + 1 mM TPM, the desensitization got faster and the peak current amplitude decreased. After the end of glycine + TPM pulses, off-currents occurred, suggestive for a specific channel block mechanism.
甘氨酸受体通道是五聚体配体门控离子通道，通过开放氯离子选择性中央孔来响应抑制性神经递质的作用。托吡酯（TPM）是一种广谱抗癫痫药物，用作局灶性癫痫发作的附加治疗或单药治疗。在本研究中，在表达α1β甘氨酸受体通道的HEK293细胞的外向膜片上研究了TPM与甘氨酸受体通道的相互作用。膜片钳技术与超快溶液交换相结合，使我们能够研究存在TPM时受体通道的动力学。我们的研究表明，TPM对甘氨酸受体通道没有激动或增强作用。然而，在存在1 mM甘氨酸 + 1 mM TPM的情况下，脱敏速度加快，峰值电流幅度降低。在甘氨酸 + TPM脉冲结束后，出现外向电流，提示存在特定的通道阻断机制。
