Abstract：
A number of mutations to members of several CNS potassium (K) channel families have been identified which result in rare forms of neonatal onset epilepsy, or syndromes of which one prominent characteristic is a form of epilepsy. Benign Familial Neonatal Convulsions or Seizures (BFNC or BFNS), also referred to as Self-Limited Familial Neonatal Epilepsy (SeLNE), results from mutations in 2 members of the KV7 family (KCNQ) of K channels; while generally self-resolving by about 15 weeks of age, these mutations significantly increase the probability of generalized seizure disorders in the adult, in some cases they result in more severe developmental syndromes. Epilepsy of Infancy with Migrating Focal Seizures (EIMSF), or Migrating Partial Seizures of Infancy (MMPSI), is a rare severe form of epilepsy linked primarily to gain of function mutations in a member of the sodium-dependent K channel family, KCNT1 or SLACK. Finally, KCNMA1 channelopathies, including Liang-Wang syndrome (LIWAS), are rare combinations of neurological symptoms including seizure, movement abnormalities, delayed development and intellectual disabilities, with Liang-Wang syndrome an extremely serious polymalformative syndrome with a number of neurological sequelae including epilepsy. These are caused by mutations in the pore-forming subunit of the large-conductance calcium-activated K channel (BK channel) KCNMA1. The identification of these rare but significant channelopathies has resulted in a resurgence of interest in their treatment by direct pharmacological or genetic modulation. We will briefly review the genetics, biophysics and pharmacology of these K channels, their linkage with the 3 syndromes described above, and efforts to more effectively target these syndromes.
摘要：
已经确定了几种CNS钾（K）通道家族成员的许多突变，这些突变导致罕见形式的新生儿发作性癫痫。或综合症，其中一个突出的特征是癫痫的一种形式。良性家族性新生儿惊厥或癫痫发作（BFNC或BFNS），也称为自我限制性家族性新生儿癫痫（SeLNE），KV7家族（KCNQ）的2个成员的K通道的突变的结果;虽然一般自我解决约15周龄，这些突变显著增加了成人全身性癫痫的可能性，在某些情况下，它们会导致更严重的发育综合征。婴儿期癫痫伴迁移局灶性癫痫发作（EIMSF），或迁移部分婴儿癫痫发作(MMPSI)，是一种罕见的严重癫痫形式，主要与钠依赖性K通道家族成员的功能获得突变有关，KCNT1或SLACK。最后,KCNMA1信道病，包括梁王综合征（LIWAS），是罕见的神经症状组合，包括癫痫发作，运动异常，发育迟缓和智力障碍，梁王综合征是一种极其严重的多形性畸形综合征，伴有包括癫痫在内的许多神经系统后遗症。这些是由大电导钙激活的K通道（BK通道）KCNMA1的成孔亚基中的突变引起的。对这些罕见但重要的通道病的鉴定已导致对通过直接药理或遗传调节进行治疗的兴趣重新兴起。我们将简要回顾遗传学，这些K通道的生物物理学和药理学，它们与上述3种综合征的联系，以及更有效地针对这些综合症的努力。
