Activity-Dependent Transcriptional Regulation of M-Type (Kv7) K+ Channels by AKAP79/150-Mediated NFAT Actions

作者：Zhang Jie; Shapiro Mark S^*

来源：Neuron, 2012, 76(6): 1133-1146.

DOI：10.1016/j.neuron.2012.10.019

M-type K+ channels, encoded by KCNQ2-KCNQ5 genes, play key roles in regulation of neuronal excitability; however, less is known about the mechanisms controlling their transcriptional expression. Here, we discovered a mechanism regulating KCNQ2/3 transcriptional expression by neuronal activity in rodent neurons, involving activation of calcineurin and nuclear factor of activated T cell (NFAT) transcription factors, orchestrated by A kinase-anchoring protein (AKAP)79/150. The signal requires Ca2+ influx through L-type Ca2+ channels and both local and global Ca2+ elevations. We postulate increased M-channel expression to act as a negative feedback to suppress neuronal hyperexcitability, demonstrated by profoundly upregulated KCNQ2/3 transcription in hippocampi from wild-type, but not AKAP150(-/-), mice after drug-induced seizures. Thus, we suggest a distinct role of AKAP79/150 and the complex it organizes in activity-dependent M-channel transcription, which may potentially serve throughout the nervous system to limit overexcitability associated with disease states such as epilepsy.

• 出版日期2012-12-20