Insight into T-type calcium channel structure, function and modulation

Low voltage-activated (LVA) T-type calcium channels are characterized by transient current and low threshold spikes (LTS), which in turn triggers neuronal firing and oscillatory behavior. Combined with their preferential localization in dendrites and their specific "window current", T-type calcium channels are considered to be key players in signal amplification and synaptic integration. Assisted by the developing pharmacological tools, the structural determinants in channel gating and kinetics, as well as novel physiological and pathological functions of T-type calcium channels are rapidly being uncovered. In this review, we provide an overview of structural determinants in T-type calcium channels, their involvement in disorders and diseases, the development of novel channel modulators, as well as structure-activity relationship (SAR) studies that lead to rational drug design