KCNQ2 and KCNQ3 pathogenic channel variants have been associated with a spectrum of developmentally regulated diseases that vary in age of onset, severity, and whether it is transient (i.e., benign familial neonatal seizures) or long-lasting (i.e., developmental and epileptic encephalopathy). KCNQ2 and KCNQ3 channels have also emerged as a target for novel antiepileptic drugs as their activation could reduce epileptic activity. Consequently, a great effort has taken place over the last 2 decades to understand the mechanisms that control the assembly, gating, and modulation of KCNQ2 and KCNQ3 channels. The current view that KCNQ2 and KCNQ3 channels assemble as heteromeric channels (KCNQ2/3) forms the basis of our understanding of KCNQ2 and KCNQ3 channelopathies and drug design. Here, we review the evidence that supports the formation of KCNQ2/3 heteromers in neurons. We also highlight functional and transcriptomic studies that suggest channel composition might not be necessarily fixed in the nervous system, but rather is dynamic and flexible, allowing some neurons to express KCNQ2 and KCNQ3 homomers. We propose that to fully understand KCNQ2 and KCNQ3 channelopathies, we need to adopt a more flexible view of KCNQ2 and KCNQ3 channel stoichiometry, which might differ across development, brain regions, cell types, and disease states.
Dev Neurosci

中文翻译：

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灵活的化学计量：对 KCNQ2 和 KCNQ3 相关神经发育障碍的影响

KCNQ2 和 KCNQ3 致病通道变异与一系列发育调节的疾病相关，这些疾病的发病年龄、严重程度以及是短暂的（即良性家族性新生儿癫痫发作）还是长期的（即发育性和癫痫性脑病）有所不同. KCNQ2 和 KCNQ3 通道也已成为新型抗癫痫药物的靶点，因为它们的激活会降低癫痫活性。因此，在过去的 2 年中，人们付出了巨大的努力来了解控制 KCNQ2 和 KCNQ3 通道的组装、门控和调制的机制。目前关于 KCNQ2 和 KCNQ3 通道组装为异聚通道 (KCNQ2/3) 的观点构成了我们理解 KCNQ2 和 KCNQ3 通道病变和药物设计的基础。这里，我们回顾了支持在神经元中形成 KCNQ2/3 异聚体的证据。我们还强调了功能和转录组学研究，这些研究表明通道组成可能不一定固定在神经系统中，而是动态和灵活的，允许一些神经元表达 KCNQ2 和 KCNQ3 同聚体。我们建议，为了充分了解 KCNQ2 和 KCNQ3 通道病，我们需要对 KCNQ2 和 KCNQ3 通道化学计量采用更灵活的观点，这可能因发育、脑区、细胞类型和疾病状态而异。
开发神经科学