title: Activity-dependent transcriptional regulation of M-Type (Kv7) K(+) channels by AKAP79/150-mediated NFAT actions.
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.
authors.affiliation: Department of Physiology, MS 7756, University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Mark S
authors.initials: MS
authors.lastname: Shapiro
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D000818:Animals; D019703:Calcineurin / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051658:KCNQ2 Potassium Channel / Q000378:metabolism*; D051659:KCNQ3 Potassium Channel / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: D054758:A Kinase Anchor Proteins; C520665:Akap5 protein, mouse; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D050778:NFATC Transcription Factors; D019703:Calcineurin