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J Neurophysiol (August 20, 2008). doi:10.1152/jn.90346.2008
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Submitted on March 9, 2008
Revised on August 8, 2008
Accepted on August 8, 2008

Coupling of L-type Ca2+ Channels to KV7/KCNQ Channels Creates a Novel, Activity-Dependent, Homeostatic Intrinsic Plasticity

Wendy W. Wu1*, C. Savio Chan2, D. James Surmeier3, and John F Disterhoft4

1 Oregon Health & Science University
2 Northwestern University Feinberg School of Medicine
3 Northwestern University
4 Northwestern University School of Medicine

* To whom correspondence should be addressed. E-mail: wuwendy{at}ohsu.edu.

Experience-dependent modification in the electrical properties of central neurons is a form of intrinsic plasticity that occurs during development and has been observed following behavioral learning. We report a novel form of intrinsic plasticity in hippocampal CA1 pyramidal neurons mediated by the KV7/KCNQ and CaV1/L-type Ca2+ channels. Enhancing Ca2+ influx with a conditioning spike train (30Hz, 3-s) potentiated the KV7/KCNQ channel function and led to a long lasting, activity-dependent increase in spike frequency adaptation-a gradual reduction in the firing frequency in response to sustained excitation. These effects were abolished by specific blockers for CaV1/L-type Ca2+ channels, KV7/KCNQ channels, and protein kinase A (PKA). Considering the widespread expression of these two channel types, the influence of Ca2+ influx and subsequent activation of PKA on KV7/KCNQ channels may represent a generalized principle in fine tuning the output of central neurons that promotes stability in firing-an example of homeostatic regulation of intrinsic membrane excitability.




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