T-type Ca²⁺ channels in normal and abnormal brain functions

Low-voltage-activated T-type Ca²⁺ channels are widely expressed in various types of neurons. Once deinactivated by hyperpolarization, T-type channels are ready to be activated by a small depolarization near the resting membrane potential and, therefore, are optimal for regulating the excitability and electroresponsiveness of neurons under physiological conditions near resting states. Ca²⁺ influx through T-type channels engenders low-threshold Ca²⁺ spikes, which in turn trigger a burst of action potentials. Low-threshold burst firing has been implicated in the synchronization of the thalamocortical circuit during sleep and in absence seizures. It also has been suggested that T-type channels play an important role in pain signal transmission, based on their abundant expression in pain-processing pathways in peripheral and central neurons. In this review, we will describe studies on the role of T-type Ca²⁺ channels in the physiological as well as pathological generation of brain rhythms in sleep, absence epilepsy, and pain signal transmission. Recent advances in studies of T-type channels in the control of cognition will also be briefly discussed.