Effects of topiramate on sodium-dependent action-potential firing by mouse spinal cord neurons in cell culture
Effects of topiramate on sodium-dependent action-potential firing by mouse spinal cord neurons in cell culture
复制标题
DOI：
10.1111/j.1528-1157.2000.tb06043.x
复制
发表时间：
2000-01-01
期刊：
影响因子：
5.6
通讯作者：
Wamil, AW
中科院分区：
文献类型：
--
作者：
McLean, MJ;Bukhari, AA;Wamil, AW
目的：利用培养的小鼠脊髓神经细胞，研究托吡酯(TPM)对钠依赖动作电位的影响。方法：测定托吡酯(TPM)抑制(阻断)去极化诱发的小鼠脊髓神经元自发重复放电(SRF)的能力，并与苯妥英(PHT)和拉莫三嗪(LTG)的作用进行比较。结果：托吡酯在大于或等于3mU M时，对SRF产生电压敏感性和时间依赖性的抑制，并伴随着动作电位上行速度的减慢。在高浓度(30-600微米)时，TPM可迅速阻断约三分之一受试者的SRF，而不影响约三分之一的SRF。在一些神经元中，TPM引起SRF间歇性限制(大约30%的神经元)或仅在几秒钟后阻断SRF(大约10%)。这种复杂的作用模式明显不同于PHT和LTG的作用模式，后者的作用总是迅速限制或完全阻断SRF。TPM与其他抗惊厥药物的另一个不同之处在于，TPM的作用更依赖于神经元接触化合物的时间长短和神经元活动的强度或持续时间。结论：本研究结果不支持NAT通道阻断是TPM抗惊厥作用的主要机制的观点。
Purpose: The effects of topiramate (TPM) on sodium-dependent action potentials were studied by using cultured mouse spinal cord neurons.Methods: The ability of TPM to limit (block) depolarization-induced spontaneous repetitive firing (SRF) was determined and compared with corresponding effects of phenytoin (PHT) and lamotrigine (LTG) in cultured mouse spinal neurons.Results: Topiramate at concentrations of greater than or equal to 3 mu M caused a voltage-sensitive and lime-dependent limitation of SRF that was associated with a decrease in the velocity of the upstroke of the action potential. At high concentrations (30-600 mu M), TPM rapidly blocked SRF in about one third of the neurons tested and did not affect SRF in about one third. In some neurons, TPM caused an intermittent limitation (sputtering) of SRF (approximate to 30% of the neurons) or blocked SRF only after a delay of several seconds (approximate to 10%). This complex pattern of effects is distinctly different from that of PHT and LTG, in which the effect was always a rapid limitation or complete blockade of SRF. Another difference between TPM and the other anticonvulsants (AEDs) is that the effects of TPM were more dependent on the length of time the neurons were exposed to the compound and the intensity or duration of neuronal activity.Conclusions: The results of this study do not support the concept that Nat channel blockade is the primary mechanism responsible for the anticonvulsant activity of TPM.