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J Neurophysiol. 2008 Oct;100(4):1897-908. doi: 10.1152/jn.90346.2008. Epub 2008 Aug 20.

Coupling of L-type Ca2+ channels to KV7/KCNQ channels creates a novel, activity-dependent, homeostatic intrinsic plasticity.

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Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.


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 (30 Hz, 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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