Coupling of L-type Ca²⁺ channels to K_V7/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 K _V7/KCNQ and Ca_V1/L-type Ca²⁺ channels. Enhancing Ca²⁺ influx with a conditioning spike train (30 Hz, 3 s) potentiated the K_V7/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 Ca_V1/L-type Ca²⁺ channels, K_V7/KCNQ channels, and protein kinase A (PKA). Considering the widespread expression of these two channel types, the influence of Ca ²⁺ influx and subsequent activation of PKA on K_V7/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.