| First Author | Zhang J | Year | 2012 |
| Journal | Neuron | Volume | 76 |
| Issue | 6 | Pages | 1133-46 |
| PubMed ID | 23259949 | Mgi Jnum | J:197655 |
| Mgi Id | MGI:5494226 | Doi | 10.1016/j.neuron.2012.10.019 |
| Citation | Zhang J, et al. (2012) Activity-dependent transcriptional regulation of M-Type (Kv7) K(+) channels by AKAP79/150-mediated NFAT actions. Neuron 76(6):1133-46 |
| abstractText | 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. |
