Coupling of L-Type Ca Channels to KV7/KCNQ Channels Creates a Novel, Activity-Dependent, Homeostatic Intrinsic Plasticity

Wu WW, Chan CS, Surmeier DJ, Disterhoft JF. Coupling of L-type Ca channels to KV7/KCNQ channels creates a novel, activity-dependent, homeostatic intrinsic plasticity. J Neurophysiol 100: 1897–1908, 2008. First published August 20, 2008; doi:10.1152/jn.90346.2008. 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 Ca 2 channels. Enhancing Ca 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 Ca 2 channels, KV7/KCNQ channels, and protein kinase A (PKA). Considering the widespread expression of these two channel types, the influence of Ca 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.