Coupling of L-type Ca2+ channels to KV7/KCNQ channels creates a novel, activity-dependent, homeostatic intrinsic plasticity.
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.
Wu
Wendy W
WW
Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. wuwendy@ohsu.edu
Chan
C Savio
CS
Surmeier
D James
DJ
Disterhoft
John F
JF
D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051656:KCNQ Potassium Channels / Q000502:physiology*; D008024:Ligands; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020746:Calcium Channels, L-Type; D051656:KCNQ Potassium Channels; D008024:Ligands; D017868:Cyclic AMP-Dependent Protein Kinases