The Α2δ subunit and absence epilepsy: beyond calcium channels?

Celli, Roberta and Santolini, Ines and Guiducci, Michela and van Luijtelaar, Gilles and Parisi, Pasquale and Striano, Pasquale and Gradini, Roberto and Battaglia, Giuseppe and Ngomba, Richard T. and Nicoletti, Ferdinando (2017) The Α2δ subunit and absence epilepsy: beyond calcium channels? Current Neuropharmacology, 15 . ISSN 1570-159X

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Abstract

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 α2δ 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 α2δ subunit facilitates VSCC activation. Hence, one expects that drugs that bind to, and inhibit the α2δ subunit, e.g. gabapentin and pregabalin, are protective against absence epilepsy and that mice lacking the α2δ 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 α2δ subunit develop absence seizures. This suggests that the α2δ 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 α2δ subunit in the pathophysiology of absence seizures focusing on the potential role of the α2δ ligands, thrombospondins

Keywords:?2? subunit, T-type voltage-sensitive Ca2+ channels, non-T-type voltage-sensitive Ca2+ channels, ducky mice, pregabalin, gabapentin, Absence epilepsy, thrombospondins
Subjects:B Subjects allied to Medicine > B140 Neuroscience
Divisions:College of Science > School of Pharmacy
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ID Code:26756
Deposited On:29 Mar 2017 09:02

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