Voltage Gated Ion Channels and Sleep

Ion channels are integral components of the nervous system, playing a pivotal role in shaping membrane potential, neuronal excitability, synaptic transmission and plasticity. Dysfunction in these channels, such as improper expression or localization, can lead to irregular neuronal excitability and synaptic communication, which may manifest as various behavioral abnormalities, including disrupted rest-activity cycles. Research has highlighted the significant impact of voltage gated ion channels on sleep parameters, influencing sleep latency, duration and waveforms. Furthermore, these ion channels have been implicated in the vulnerability to, and the pathogenesis of, several neurological and psychiatric disorders, including epilepsy, autism, schizophrenia, and Alzheimer’s disease (AD). In this comprehensive review, we aim to provide a summary of the regulatory role of three predominant types of voltage-gated ion channels—calcium (Ca²⁺), sodium (Na⁺), and potassium (K⁺)—in sleep across species, from flies to mammals. We will also discuss the association of sleep disorders with various human diseases that may arise from the dysfunction of these ion channels, thereby underscoring the potential therapeutic benefits of targeting specific ion channel subtypes for sleep disturbance treatment.