Ricerc@Sapienza

Spike-wave discharges, underlying absence seizures, are generated within a cortico-thalamo-cortical network that involves the somatosensory cortex, the reticular thalamic nucleus, and the ventrobasal thalamic nuclei. Activation of T-type voltage-sensitive calcium channels (VSCCs) contributes to the pathological oscillatory activity of this network, and some of the first-line drugs used in the treatment of absence epilepsy inhibit T-type calcium channels. The ?2? subunit is a component of high voltage-activated VSCCs (i.e., L-, N-, P/Q-, and R channels) and has also been found to be associated with T channels. The presence of the ?2? subunit facilitates VSCC activation. Hence, one expects that drugs that bind to, and inhibit the ?2? subunit, e.g. gabapentin and pregabalin, are protective against absence epilepsy and that mice lacking the ?2? subunit are resistant to evoked absence seizures. In contrast, gabapentin and pregabalin are not clinically useful and may even be detrimental in the treatment of absence epilepsy, and ducky mice lacking the ?2? subunit develop absence seizures. This suggests that the ?2? subunit displays functions that go beyond the regulation of VSCCs, and that these functions are involved in the regulation of the cortico-thalamo-cortical network. This viewpoint critically examines the role of the ?2? subunit in the pathophysiology of absence seizures focusing on the potential role of the ?2? ligands, thrombospondins.