Referenced in: none

Automatically associated channels: Kv7.2 , Kv7.5

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

Authors: Jie Zhang, Mark S Shapiro

Journal, date & volume: Neuron, 2012 Dec 20 , 76, 1133-46

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23259949

Abstract
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.