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Neuron. 2012 Dec 20;76(6):1133-46. doi: 10.1016/j.neuron.2012.10.019.

Activity-dependent transcriptional regulation of M-Type (Kv7) K(+) channels by AKAP79/150-mediated NFAT actions.

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Department of Physiology, MS 7756, University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.


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 Ca(2+) influx through L-type Ca(2+) channels and both local and global Ca(2+) 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.

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