Fast and slow Ca2+-dependent hyperpolarization mechanisms connect membrane potential and sleep homeostasis.

Several lines of evidence indicate that the sleep-wake state of cortical neurons is regulated not only through neuronal projections from the lower brain, but also through the cortical neurons' intrinsic ability to initiate a slow firing pattern related to the slow-wave oscillation observed in electroencephalography of the sleeping brain. Theoretical modeling and experiments with genetic and pharmacological perturbation suggest that ion channels and kinases acting downstream of calcium signaling regulate the cortical-membrane potential and sleep duration. In this review, we introduce possible Ca2+-dependent hyperpolarization mechanisms in cortical neurons, in which Ca2+ signaling associated with neuronal excitation evokes kinase cascades, and the activated kinases modify ion channels or pumps to regulate the cortical sleep/wake firing mode.