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Transcriptional control of KCNQ channel genes and the regulation of neuronal excitability

Journal Article


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Abstract


  • Regulation of the resting membrane potential and the repolarization of neurons are important in regulating neuronal excitability. The potassium channel subunits Kv7.2 and Kv7.3 play a key role in stabilizing neuronal activity. Mutations in KCNQ2 and KCNQ3, the genes encoding Kv7.2 and Kv7.3, cause a neonatal form of epilepsy, and activators of these channels have been identified as novel antiepileptics and analgesics. Despite the observations that regulation of these subunits has profound effects on neuronal function, almost nothing is known about the mechanisms responsible for controlling appropriate expression levels. Here we identify two mechanisms responsible for regulating KCNQ2 and KCNQ3 mRNA levels. We show that the transcription factor Sp1 activates expression of both KCNQ2 and KCNQ3, whereas the transcriptional repressor REST (repressor element 1-silencing transcription factor) represses expression of both of these genes. Furthermore, we show that transcriptional regulation of KCNQ genes is mirrored by the correlated changes in M-current density and excitability of native sensory neurons. We propose that these mechanisms are important in the control of excitability of neurons and may have implications in seizure activity and pain.

Authors


  •   Mucha, Mariusz (external author)
  •   Ooi, Lezanne
  •   Linley, John (external author)
  •   Mordaka, Pawel (external author)
  •   Dalle, Carine (external author)
  •   Robertson, Brian (external author)
  •   Gamper, Nikita (external author)
  •   Wood, Ian C. (external author)

Publication Date


  • 2010

Citation


  • Mucha, M., Ooi, L., Linley, J., Mordaka, P., Dalle, C., Robertson, B., Gamper, N. & Wood, I. C. (2010). Transcriptional control of KCNQ channel genes and the regulation of neuronal excitability. The Journal of Neuroscience, 30 (40), 13235-13245.

Scopus Eid


  • 2-s2.0-77957736469

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=8002&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/4659

Has Global Citation Frequency


Number Of Pages


  • 10

Start Page


  • 13235

End Page


  • 13245

Volume


  • 30

Issue


  • 40

Place Of Publication


  • United States

Abstract


  • Regulation of the resting membrane potential and the repolarization of neurons are important in regulating neuronal excitability. The potassium channel subunits Kv7.2 and Kv7.3 play a key role in stabilizing neuronal activity. Mutations in KCNQ2 and KCNQ3, the genes encoding Kv7.2 and Kv7.3, cause a neonatal form of epilepsy, and activators of these channels have been identified as novel antiepileptics and analgesics. Despite the observations that regulation of these subunits has profound effects on neuronal function, almost nothing is known about the mechanisms responsible for controlling appropriate expression levels. Here we identify two mechanisms responsible for regulating KCNQ2 and KCNQ3 mRNA levels. We show that the transcription factor Sp1 activates expression of both KCNQ2 and KCNQ3, whereas the transcriptional repressor REST (repressor element 1-silencing transcription factor) represses expression of both of these genes. Furthermore, we show that transcriptional regulation of KCNQ genes is mirrored by the correlated changes in M-current density and excitability of native sensory neurons. We propose that these mechanisms are important in the control of excitability of neurons and may have implications in seizure activity and pain.

Authors


  •   Mucha, Mariusz (external author)
  •   Ooi, Lezanne
  •   Linley, John (external author)
  •   Mordaka, Pawel (external author)
  •   Dalle, Carine (external author)
  •   Robertson, Brian (external author)
  •   Gamper, Nikita (external author)
  •   Wood, Ian C. (external author)

Publication Date


  • 2010

Citation


  • Mucha, M., Ooi, L., Linley, J., Mordaka, P., Dalle, C., Robertson, B., Gamper, N. & Wood, I. C. (2010). Transcriptional control of KCNQ channel genes and the regulation of neuronal excitability. The Journal of Neuroscience, 30 (40), 13235-13245.

Scopus Eid


  • 2-s2.0-77957736469

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=8002&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/4659

Has Global Citation Frequency


Number Of Pages


  • 10

Start Page


  • 13235

End Page


  • 13245

Volume


  • 30

Issue


  • 40

Place Of Publication


  • United States